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Pesticide-Induced Diseases: Cancer

Bladder CancerBone CancerBrain CancerCervical CancerColorecatal CancerEye CancerGallbladder CancerKidney/Renal CancerLarynx CancerLeukemiaLip CancerLiver/Hepatic CancerLung CancerLymphomaMelanomaMouth CancerMultiple MyelomaNeuroblastomaOesophageal CancerOvarian CancerPancreatic CancerProstate CancerSoft Tissue SarcomaStomach CancerSinonasal Cancer ● Testicular CancerThyroid CancerUteran Cancer

The link between pesticides and cancer has long been a concern. While agriculture has traditionally been tied to pesticide-related illnesses, 19 of 30 commonly used lawn pesticides and 28 of 40 commonly used school pesticides are linked to cancer. Even with the growing body of evidence linking environmental exposures to cancer in recent years, a report released May 6, 2010 by the President’s Cancer Panel finds that the true burden of environmentally-induced cancer is greatly underestimated. The Panel’s report, Reducing Environmental Cancer Risk: What We Can Do Now, concludes that while environmental exposure is not a new front on the war on cancer, the grievous harm from carcinogenic chemical use has not been addressed adequately by the nation’s cancer program.

Bladder Cancer

  • Occupational exposure to pesticides and bladder cancer risk.
    Study used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. Results found associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr and imazaquin, which are aromatic amines. Ever use of imazaquin was associated with increased risk whereas the excess risk among users of imazethapyr was evident among never smokers. Study also observed increased risks overall and among never smokers for use of several chlorinated pesticides including chlorophenoxy herbicides and organochlorine insecticides. Several associations between specific pesticides and bladder cancer risk were observed, many of which were stronger among never smokers, suggesting that possible risk factors for bladder cancer may be more readily detectable in those unexposed to potent risk factors like tobacco smoke.
    [Koutros S, Silverman DT, Alavanja MC, Andreotti G, et al. 2015. Int J Epidemiol. pii: dyv195.]
  • Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers.
    This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H:
    quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Exposure to pesticides was associated with increased bladder cancer risk: 1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.
    [Amr S, Dawson R, Saleh DA, Magder LS, et al. 2015. Arch Environ Occup Health. 70(1):19-26.]
  • Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.
    Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. Authors show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.
    [Da Rocha MS, Arnold LL, De Oliveira ML, Catalano SM, et al. 2014. Crit Rev Toxicol. 44(5):393-406.]
  • Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.
    Study investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls.The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects.
    [Matic MG, Coric VM, Savic-Radojevic AR, et al. 2014. PLoS One. 9(6):e99448.]
  • Gene environment interaction in urinary bladder cancer with special reference to organochlorine pesticide: a case control study.
    Urinary bladder cancer (UBC) is a common disease worldwide with a higher incidence rate in developed countries. Organochlorine pesticides (OCPs), potent endocrine disrupters, are found to be associated with several cancers such as prostate, breast, bladder, etc. The present study was carried out in UBC subjects and healthy control subjects with an aim to determine the role of Glutathione S-transferase (GST) and GSTT1 polymorphism and its implication on the OCP detoxification or bioaccumulation which may increase the risk of UBC in humans. This study was also designed to identify the "gene-environment interaction" specifically between gene polymorphism in xenobiotic metabolizing genetic enzyme(s) and blood OCP levels. The results demonstrated a significant increase in frequency of GSTM1/GSTT1(null) genotype in UBC cases without interfering the distribution of other GSTT1/GSTM1 genotypes. Findings indicate that "gene-environment interaction" may play a key role in increasing the risk for UBC in individuals who are genetically more susceptible due to presence of GSTM1/GSTT1 null deletion during their routine encounter with or exposure to OCPs.
    [Sharma T, Jain S, Verma A et al. 2013. Cancer Biomark.13(4):243-51]
  • Heterocyclic aromatic amine pesticide use and human cancer risk: results form the U.S. Agricultural Health Study
    A prospective cohort study of the Agricultural Health Study evaluated imazethapyr, a heterocyclic aromatic amine herbicide, finding significant trend in risk with increasing lifetime exposure for bladder cancer, limited to proximal cancers.
    [Koutros, S., et al. 2009. Int J Cancer 124(5):1206-1212.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for bladder cancer in males (OR 1.71).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a possible relationship between fruit crops and colon and bladder cancer.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]

Bone Cancer

  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe
    A nuliticentric case-control study in 7 European countries finds that individuals that have ever used pesticides have over a two-fold increase risk of bone sarcoma (OR 2.33), yet the study finds that duration of use of pesticides showend no increase trend in the risk.
    [Merietti, F., et al. 2006. Int J Cancer 118(3):721-727.]
  • Parental occupational exposures and Ewing’s sarcoma
    A NIH case-control study finds that although exposure to pesticides is not significantly associated with Ewing’s sarcoma, a higtory of household pesticide extermination is associated with ES among boy aged 15 years or younger (OR 3.0).
    [Moore, L.E., et al. 2005. Int J Cancer 114(3):472-478.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for bone cancer in males (OR 1.81).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]
  • Ewing’s bone sarcoma, paternal occupational exposure, and other factors
    A study of Ewing’s bone sarcoma patients shows an elevated risk for children whose fathers are engaged in agricultural occupations during the period from six months prior to conception of the patient to the time of diagnosis (8.8 OR) and for children whose fathers had occupational exposure to herbicides, pesticides, or fertilizers (6.1 OR).
    [Holly, E.A., at al. 1992. Am J Epidemiol 135(2):122-129.]

Brain Cancer

Childhood Brain Cancer

  • Increased risk of childhood brain tumors among children whose parents had farm-related pesticide exposures during pregnancy.
    Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. Authors performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Findings of meta-analyses revealed a significantly increased risk of CBT among children whose mothers had farm-related exposures during pregnancy (RR=1.48, 95% CI=1.18-1.84). A dose response was recognized when this risk estimate was compared to those for risk of CBT from maternal exposure to non-agricultural pesticides (e.g., home extermination, pest strips) during pregnancy (RR=1.36, 1.10-1.68), and risk of CBT among children exposed to agricultural activities (RR=1.32, 1.04-1.67). Three studies combined for the paternal exposure to pesticides during preconception produced a calculated summary risk estimate of odds ratio (OR) = 2.29 (95% CI: 1.39-3.78). Meta-analysis of five studies of paternal exposure to pesticides during pregnancy produced a final calculated summary risk estimate of OR = 1.63 (95% CI: 1.16-2.31). The search of the CTD databases revealed association between herbicide and astrocytoma and more than 300 genes are altered by exposure to herbicide, fungicide, insecticide or pesticides. Based on the collective results of these meta-analyses, it appears that pesticide exposure may increase risk of CBT, with preconception and prenatal exposures being especially important factors in increasing risk of its development.
    [Kunkle B, Bae S, Singh KP, Roy D. 2014. JP J Biostat. 11(2):89-101]
  • Exposure to pesticides and the risk of childhood brain tumors.
    Previous research has suggested positive associations between parental or childhood exposure to pesticides and risk of childhood brain tumors (CBT). This Australian case-control study of CBT investigated whether exposures to pesticides before pregnancy, during pregnancy and during childhood, were associated with an increased risk.Cases were recruited from 10 pediatric oncology centers, and controls by random-digit dialing, frequency matched on age, sex, and State of residence. The odds ratios (ORs) for professional pest control treatments in the home in the year before the index pregnancy, during the pregnancy, and after the child's birth were 1.54 (95% confidence interval (CI): 1.07, 2.22), 1.52 (95% CI: 0.99, 2.34) and 1.04 (95% CI: 0.75, 1.43), respectively. ORs for treatments exclusively before pregnancy and during pregnancy were 1.90 (95% CI: 1.08, 3.36) and 1.02 (95% CI: 0.35, 3.00), respectively. The OR for the father being home during the treatment was 1.79 (95% CI: 0.85, 3.80). The OR for paternal occupational exposure in the year before the child's conception was 1.36 (95% CI: 0.66, 2.80). ORs for prenatal home pesticide exposure were elevated for low- and high-grade gliomas; effect estimates for other CBT subtypes varied and lacked precision.These results suggest that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased CBT risk. It may be advisable for both parents to avoid pesticide exposure during this time.
    [Greenop KR, Peters S, Bailey HD, et al. 2013. Cancer Causes Control. 24(7):1269-78]
  • Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies
    The authors performed a meta-analysis of case-control and cohort studies to clarify the possible relationship between exposure to pesticides and childhood cancers.Two cohort and 38 case-control studies were selected for the first meta-analysis.Meta-analysis of the three cohort studies did not show any positive links between parental pesticide exposure and childhood cancer incidence. However, the meta-analysis of the 40 studies with OR values showed that the risk of lymphoma and leukaemia increased significantly in exposed children when their mother was exposed during the prenatal period. The risk of brain cancer was correlated with paternal exposure either before or after birth. The OR of leukaemia and lymphoma was higher when the mother was exposed to pesticides (through household use or professional exposure). Conversely, the incidence of brain cancer was influenced by the father's exposure (occupational activity or use of household or garden pesticides). Despite some limitations in this study, the incidence of childhood cancer does appear to be associated with parental exposure during the prenatal period.
    [Vinson F, Merhi M, Baldi I, Raynal H, et al. 2011. Occup Environ Med. 68(9):694-702.]
  • Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes
    A population-based, case control study of California and Washington state born children ten years of age or younger and functional genetic polymorphisms and parents use of home insecticide treatments finds a strong interaction between insecticide exposure during childhood and chromosome genotype PON1-108T allele (OR 1.8) and FMO1-9536A (*6) allele (OR = 2.7), suggesting that exposure in childhood to insecticides in combination with a reduced ability to detoxify them increases risk of developing brain tumors.
    [Nielsen, S.S., et al. 2010. Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes. Environmental Health Perspectives 118(1):144-149]
  • Critical Confluence: Gene Variants, Insecticide Exposure May Increase Childhood Brain Tumor Risk
    Epidemiologic data have suggested a link between pesticide exposures and childhood brain tumors. The link may be specific to insecticides such as organophosphorus and carbamate compounds, which are known to target the nervous system. Previously published work investigated the role of individual genetic variation with a focus on paraoxonase (PON1), a key enzyme in the metabolism of organophosphorus insecticides commonly used in homes at the time but now banned for residential use. This work showed that children with brain tumors were more likely to carry a common single-nucelotide polymorphism (SNP) gene variant in the promoter region of the PON1 gene (PON1C-108T) than other children, and that the association between this SNP and brain tumors was stronger in children with a history of home insecticide exposure. Research in an expanded study population now provides additional evidence that exposure to insecticides, paired with specific metabolism gene variants, may increase the risk of childhood brain tumors.
    [Barrett, J. 2010. Environ Health Perspect. 118(1): A35]
  • Parental exposure to pesticides and childhood brain cancer: U.S. Atlantic coast childhood brain cancer study.
    The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use. Study aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children. Authors included 526 one-to-one-matched case-control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. Using information on residential pesticide use and jobs held by fathers during the 2-year period before the child's birth, authors assessed potential exposure to insecticides, herbicides, and fungicides. A significant risk of astrocytoma was associated with exposures to herbicides from residential use. Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.
    [Shim YK, Mlynarek SP, van Wijngaarden E. 2009.Environ Health Perspect. 117(6):1002-6.]
  • A case-control study of childhood brain tumors and fathers' hobbies: a Children's Oncology Group study
    A case-control study evaluating parental risk factors for childhood brain tumors finds a significant association for home lawn care pesticide applications during pregnancy (OR 1.6) and after birth (OR 1.8) and thus pesticides may increase the risk of medulloblastoma and primitive neuroectodermal tumors in children.
    [Rosso, A.L., et al. 2008. Cancer Causes Control 19(10)1201-1207]
  • The Upper Midwest Health Study: a case-control study of primary intracranial gliomas in farm and rural residents.
    A NIOSH population based case control study finds moving to a farm as an adolescent (between the ages of 11 and 20), rather than moving to a farm as an adult, is associated with a greater risk for gliomas.
    [Ruder, A.M., et al. 2006. J Agric Saf Health 12(4):255-274]
  • Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1).
    Prior research suggests that childhood brain tumors (CBTs) may be associated with exposure to pesticides. Organophosphorus insecticides (OPs) target the developing nervous system, and until recently, the most common residential insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate whether two common PON1 polymorphisms, C-108T and Q192R, are associated with CBT occurrence, authors conducted a population-based study of 66 cases and 236 controls using DNA from neonatal screening archive specimens in Washington State, linked to interview data. The risk of CBT was nonsignificantly increased in relation to the inefficient PON1 promoter allele [per PON1(-108T) allele, relative to PON1(-108CC): odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2; p-value for trend = 0.07]. Notably, this association was strongest and statistically significant among children whose mothers reported chemical treatment of the home for pests during pregnancy or childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95% CI, 1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and for primitive neuroectodermal tumors (per PON1(-108T) allele: OR = 2.4; 95% CI, 1.1-5.4). Larger studies that measure plasma PON1 levels and incorporate more accurate estimates of pesticide exposure will be required to confirm these observations.
    [Searles Nielsen S, Mueller BA, De Roos AJ, et al. 2005. Environ Health Perspect.113(7):909-13.]
  • Farm-related exposures and childhood brain tumours in seven countries: results from the SEARCH International Brain Tumour Study.
    A population based, case control study finds that maternal exposure, during the 5 years proceeding the child’s birth, is related to childhood brain tumors, relative to maternal exposure to agricultural pesticides.
    [Efird, J.T., et al. 2003. Paediatr Perinat Epidemiol 17(2):201-211]
  • Parental occupational exposure to pesticides and childhood brain cancer.
    A community-based case-control study of parental occupational pesticide exposure and childhood brain cancer finds a slightly elevated risk of astrocytoma for paternal exposure to insecticides, herbicides, and fungicides; a slightly elevated risk of primitive neuroectodermal tumors (PNET) for paternatal exposure to herbicides. The study also finds a small elevated risk for astrocytoma for maternal exposure to insecticides and non-agricultural fungicides.
    [Van Wijngaarden, E., et al. 2003. American Journal of Epidemiology 157(11):989-997]
  • Farm and animal exposures and pediatric brain tumors: results from the United States West Coast Childhood Brain Tumor Study.
    A National Cancer Institute sponsored population-based case-control finds that, although the numbers were small, mothers exposed to farm pesticides were more likely to have a child with a brain tumor.
    [Holly, E.A., et al. 1998. Cancer Epidemiol Biomarkers Prev 7(9):797-802]
  • Household pesticides and risk of pediatric brain tumors
    Prenatal exposure to flea and tick pesticides significantly increased the risk for pediatric brain tumor, especially for children less than five years old at diagnosis. Prenantal risk is highest for mothers who prepared, applied, or cleaned up the products themselves. Sprays and fogger flea and tick products showed the most significant risk.
    [Pogoda, J.M. and Preston-Martin, S. 1997. Environmental Health Perspectives 105:1214-1220]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    In a large cohort study in Norway, parental occupational agricultural use of pesticides is associated with childhood brain tumors (rate ratio (RR) 1.71) and more significantly with non-astrocytic neuroepithlial tumors (RR 3.37) in farmer’s offspring aged 0-14 years.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
  • Incidence and risk factors for childhood brain tumors in the Ile de France.
    A case-control study in France coordinated by International Agency for Research on Cancer finds a statistically significant association for farm residence and home treated with pesticides for childhood brain tumors
    [Cordier, S., et al. 1994. Int J Cancer 59(6):776-782]
  • Risk factors for astrocytic glioma and primitive neuroectodermal tumor of the brain in young children: a report from the Children's Cancer Group
    A case-control study focusing on gestational exposures find elevated risks for primitive neuroectodermal tumor (PNET), one the of the most common subtypes of brain tumors in children, for mother’s residence on a farm during pregnancy and for the child’s residence on a farm for at least one year. Mothers of astrocytoma brain cancer cases were more likely than their controls to report weekly use of insect sprays and pesticides.
    [Bunin, G.R., et al. 1994. Cancer Epidemiology, Biomarkers and Prevention 3:197-204]
  • Family pesticide use and childhood brain cancer.
    Studies show that children living in households where pesticides are used suffer elevated rates of brain cancer, for some age and pesticide specific exposures.
    [Davis, J., et al. 1993. Family pesticide use and childhood brain cancer. Archives of Environmental Contamination and Toxicology 24:87-92]
  • Parental occupation and intracranial neoplasms of childhood: results of a case-control interview study.
    A case-control study of childhood brain tumors finds paternal employment in agriculture is associated with excess risk.
    [Wilkins, J.R. and T. Sinks. 1990. Am J Epidemiol 132(2):275-292]
  • Paternal occupation and brain cancer in offspring: a mortality-based case-control study
    A mortality-based case-control study of Ohio-born children who died from brain cancer looking at paternal occupation finds that case fathers are more likely than control fathers to have been employed, at the time of the child’s birth, in agriculture.
    [Wilkins, J.R. and Koutras, R.A. 1988. Am J Ind Med 14(3):299-318]
  • Risk factors for brain tumors in children
    An exploratory case-control study in Baltimore, Maryland finds that more children with brain tumors and children with other cancers are found to have been exposed to insecticides than other children.
    [Gold, E., et al. 1979. American Journal of Epidemiology 109(3):309-319]

Adult Brain Cancer

Breast Cancer

  • Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.
    It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. The present investigation was designed to identify the pathway involved in chlorpyrifos (CPF)-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, authors determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. The molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide were also looked at. Study demonstrates that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. The main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. Study concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.
    [Ventura C, Venturino A, Miret N, et al. 2015. Chemosphere. 120:343-50.]
  • Effects of environmental organochlorine pesticides on human breast cancer: putative involvement on invasive cell ability
    POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.
    [Pestana D, Teixeira D, Faria A, Domingues V, et al. 2015. Environ Toxicol. 30(2):168-76.]
  • In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case-control study.
    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. In this work authors evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case-control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action.
    [Rivero J, Luzardo OP, Henríquez-Hernández LA, Machín RP, et al. 2015. Sci Total Environ. 537:197-202]
  • Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.
    Study examined associations between organochlorine insecticides p,p'-DDT , its primary metabolite, p,p'-DDE, and chlordane assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, authors identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.
    [Parada H Jr, Wolff MS, Engel LS, White AJ, et al. 2015. Int J Cancer. doi: 10.1002/ijc.29806]
  • Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study
    Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. This study evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).Authors observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.
    [Lerro CC, Koutros S, Andreotti G, Friesen MC, et al. 2015. Occup Environ Med. 72(10):736-44]
  • Risk of female breast cancer and serum concentrations of organochlorine pesticides and polychlorinated biphenyls: a case-control study in Tunisia
    The aim of this study was to investigate the association between serum concentrations of a group of organochlorine pesticides/polychlorinated biphenyls with xenoestrogenic potential and the risk of breast cancer in a female population from Tunisia. β-hexachlorocyclohexane (β-HCH), hexachlorobenzene, heptachlor, polychlorinated biphenyl congeners 138, 153, and 180, and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with breast cancer risk. However, when the models were further adjusted for the selected covariates, only β-HCH and p,p'-DDE remained statistically significant, and heptachlor was borderline significant. In addition, analyses using POP concentration tertiles corroborated a positive dose-response relationship that was significant for p,p'-DDE. A similar trend was also confirmed for β-HCH, in which concentrations≥limit of detection were positively associated with breast cancer risk (vs. concentrations<limit of detection, OR=3.44, p<0.05). Finally, the relative influence of each chemical in the presence of the others was assessed by entering the three chemicals in a single model with all covariates, and only β-HCH remained positively associated with the risk of cancer. Findings suggest a potential association between exposure to at least one organochlorine pesticide and breast cancer risk. However, our results should be interpreted with caution, and further research is warranted to confirm these findings.
    [Arrebola JP, Belhassen H, Artacho-Cordón F, Ghali R, Ghorbel H, et al. 2015. Sci Total Environ. 520:106-13]
  • The organochlorine pesticides residues in the invasive ductal breast cancer patients.
    75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls, and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC. The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.
    [Yang JZ, Wang ZX, Ma LH, Shen XB, et al. 2015. Environ Toxicol Pharmacol. 40(3):698-703]
  • Timing of Environmental Exposures as a Critical Element in Breast Cancer Risk
    Literature was reviewed and evidence gathered on the effects of the environment on risk of breast cancer or mammary tumor development in animal research models as it pertained to the influence of timing of exposure on later-life outcomes.Evidence has accumulated for several chemicals that environmental factors have a stronger effect on breast cancer risk when exposure occurred early in life. The insecticide, dichlorodiphenyltrichloroethane, is an excellent example and is just one of several chemicals for which there seems to be both animal and human evidence for the developmental basis of adult disease. The developing breast undergoes many changes in early life, leaving it vulnerable to the effects of epigenetic marks, endocrine disruption, and carcinogens. More research is needed in the area of early beginnings of breast cancer, with prevention of the disease as the ultimate goal.
    [Fenton S and Birnbaum, L. 2015. Endocrine Soc. http://dx.doi.org/10.1210/jc.2015-2848]
  • Assessing the underlying breast cancer risk of Chinese females contributed by dietary intake of residual DDT from agricultural soils.
    The greatest concern over DDT exposure in China arose since the early 1990s for the rising breast cancer incidence, and the cause still remains to be elucidated. An extensive survey of DDT background in agricultural soils, covered the entire region of China, was conducted. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake was modeled and estimated to be 0.34 μg/kg p,p'-DDE (the main bioactive constituent in DDT). Population attributable fraction derived from a case-control study from 78 women with breast cancer and 72 controls was used to assess the DDT exposure risk to breast cancer. Based on the estimated population attributable fraction with a median value of 0.6% (IQR 0.23-2.11%), the excess annual breast cancer incidence rate attributable to p,p'-DDE exposure averaged 0.06×10(-5) with significant spatial variations varying from 0.00021×10(-5) to 11.05×10(-5) in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited relative risk and population attributable fraction imply confounding factors for breast cancer in Chinese females.
    [Tang M, Zhao M, Zhou S, et al. 2014. Environ Int. 73:208-15]
  • Case-control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women.
    Study aimed to measure the association between exposure to select environmental chemicals and breast cancer among AN women.A case-control study of 170 women (75 cases, 95 controls) were recruited from the AN Medical Center from 1999 to 2002. Serum concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB-153, PCB-180) were lower in case women than controls. Persistent pesticides, PCBs, and most phthalate metabolites were not associated with case status in univariate logistic regression. The odds of being a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP) concentrations that were above the median. Women with oestrogen receptor (ER)-/progesterone receptor (PR)-tumour types tended to have higher concentrations of persistent pesticides than did ER+/PR+ women, although these differences were not statistically significant. Exposure to the parent compound of the phthalate metabolite MEHP may be associated with breast cancer.
    [Holmes AK, Koller KR, Kieszak SM, Sjodin A, et al. 2014. Int J Circumpolar Health. 73:25760.]
  • Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor.
    Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.
    [Medjakovic S, Zoechling A, Gerster P, et al. 2014. Environ Toxicol. 29(10):1201-16]
  • Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.
    Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. In this review authors discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).
    [Albini A, Rosano C, Angelini G, Amaro A, et al.2014. Curr Med Chem. 21(9):1129-45.]
  • Household and occupational exposure to pesticides and risk of breast cancer.
    The association between breast cancer in women and the use of household or occupational pesticides was examined in a population-based case-control study. This study was conducted in Western Australia in 2009-2011 and included 1,789 controls and 1,205 cases. Information on household pesticide exposure was collected from questionnaires. For occupational pesticide exposure, job-specific modules (JSMs) were used. Women's exposures to pesticides in households and workplaces were not related to increased risk of breast cancer. The prevalence of occupational exposure to pesticides among women in our study was low. In the stratified analyses, the odd ratios associated with household pesticide use were similar among participants who believed pesticides increased breast cancer risk and those who did not. The results of our study did not show associations between breast cancer and household or occupational exposure to pesticides.
    [El-Zaemey S, Heyworth J, Glass DC, 2014. Int J Environ Health Res. 24(2):91-102]
  • DDT/DDE and breast cancer: a meta-analysis.
    The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE. Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls. No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans.
    [Ingber SZ, Buser MC, Pohl HR, et al. 2013. Regul Toxicol Pharmacol. 67(3):421-33]
  • Glyphosate induces human breast cancer cells growth via estrogen receptors.
    This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.
    [Thongprakaisang S, Thiantanawat A, Rangkadilok N, et al. 2013. Food Chem Toxicol.59:129-36]
  • Noticing pesticide spray drift from agricultural pesticide application areas and breast cancer: a case-control study.
    Study examined the relationship between self-reported noticing of pesticide spray drift from agricultural areas and breast cancer. A case-control study of breast cancer was conducted in Western Australia from 2009 to 2011. Awareness of pesticide spray drift from agricultural areas was assessed by a self-report of whether the participant had noticed spray drift. This analysis included 1,743 controls and 1,169 cases. Among women who reported 'ever noticed' pesticide spray drift from agricultural areas, an increased risk of breast cancer was also observed. A dose response relationship between lifetime exposure to noticing pesticide spray drift and risk of breast cancer was observed. An increased risk of breast cancer was observed among women who noticed pesticide spray drift: initially at the age of 20 or younger; at least 20 years before diagnosis; and for 10 years or more. These findings support the hypothesis that women who ever noticed spray drift or who first noticed spray drift at a younger age had increased risk of breast cancer.
    [El-Zaemey S, Heyworth J, Fritschi L. 2013. Aust N Z J Public Health.37(6):547-55.]
  • Complex organochlorine pesticide mixtures as determinant factor for breast cancer risk: a population-based case-control study in the Canary Islands (Spain)
    This population-based study was designed to evaluate the profile of mixtures of organochlorines detected in 103 healthy women and 121 women diagnosed with breast cancer from Gran Canaria Island, and the relation between the exposure to these compounds and breast cancer risk.The most prevalent mixture of organochlorines among healthy women was the combination of lindane and endrin, and this mixture was not detected in any affected women. Breast cancer patients presented more frequently a combination of aldrin, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), and this mixture was not found in any healthy woman. After adjusting for covariables, the risk of breast cancer was moderately associated with DDD (OR = 1.008, confidence interval 95% 1.001-1.015, p = 0.024).This study indicates that healthy women show a very different profile of organochlorine pesticide mixtures than breast cancer patients, suggesting that organochlorine pesticide mixtures could play a relevant role in breast cancer risk.
    [Boada LD, Zumbado M, Henríquez-Hernández LA, et al. 2012. Environ Health. 11:28]
  • In vitro effects of herbicides and insecticides on human breast cells.
    Authors examined the cytotoxicity of more environmentally relevant concentrations of four herbicides, acetochlor, atrazine, cyanazine, and simazine, and two insecticides, chlorpyrifos and resmethrin, in three human breast cell lines. Interestingly, cytotoxicity was not observed in the estrogen-dependent MCF-7 mammary epithelial carcinoma cells; rather increases in cell viability were seen for some of the compounds at select concentrations. These results vary greatly from what was observed in the estrogen independent MDA-MB-231 breast cancer cells and the non-cancerous MCF-10A breast cells. This gives insight into how different tumors may respond to pesticide exposure and allows us to make more accurate conclusions about the potential cytotoxicity or, at times, stimulatory actions of these pesticides.
    [Rich JD, Gabriel SM, Schultz-Norton JR. 2012. ISRN Toxicol. 2012:232461]
  • Synergistic effect of malathion and estrogen on mammary gland carcinogenesis.
    Breast cancer is the most frequent malignancy diagnosed in women and is a classical model of hormone-dependent malignancy. Over the past 15-20 years, epidemiological studies have pointed to an increased breast cancer risk associated with prolonged exposure to female hormones. On the other hand, environmental chemicals such as malathion, an organophosphorous pesticide used to control a wide range of sucking and chewing pests of field crops, may be involved in the etiology of breast cancers. Results indicated that estrogen alone increased average number of lobules per mm2 of rat mammary glands in comparison to control and malathion alone at 30, 124, 240 and 400 days after 5-day treatments. On the other hand, malathion alone significantly increased the number of ducts in stage of proliferation at 10-240 days after 5-day treatments. Furthermore, markers for cancer detection such as mutant p53, c-myc, c-fos and CYPs proteins were overexpressed after treatments. Atropine, an anticholinergic drug, counteracted these effects when it was combined with malathion under similar conditions. The combination of malathion and estrogen synergistically increased number of lobules and ducts per mm2 of rat mammary glands after treatments and inducing mammary cancer. It can be concluded that combination of an environmental substance such as the pesticide malathion and an endogenous substance such as estrogen can enhance the deleterious effects in human mammary glands inducing cancer and atropine is able to diminish these effects.
    [Calaf GM and Echiburú-Chau C. 2012. Oncol Rep. 28(2):640-6.]
  • Environmental exposure and breast cancer among young women in Rio de Janeiro, Brazil
    A case series study in Brazil find an increased risk of breast cancer for residential use of pesticides during adulthood.
    [Ortega Jacome, G.P., et al. 2010. J Toxicol Environ Health A. 73(13-14):858-65.]
  • Environmental Oestrogens and Breast Cancer: Evidence for Combined Involvement of Dietary, Household and Cosmetic Xenoestrogens
    Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.
    [Darbre, P and Charles, A. 2010. Anticancer Research. 30(3): 815-827]
  • Pesticides and breast cancer risk: a comparison between developed and developing countries
    Literature review links DDT to breat cancer in the developing world. According to the authors, there is a dearth of studies in developing countries, which cannot be made up for generalizing the results from developed countries to the developing and third world.
    [Shakeel MK, George PS, Jose J, Jose J, Mathew A. 2010. Asian Pac J Cancer Prev. 2010;11(1):173-80.]
  • Reported residential pesticide use and breast cancer risk on Long Island, New York
    A population based, case control study of Long Island, New York breast cancer cases finds an increased risk associated with: (a) lifetime residential pesticide use (OR 1.39); (b) application of lawn insecticides themselves (OR 1.56) and is higher if it is in liquid form (OR 1.77) or a combination of product type for outdoor plants (OR 1.83); (c) professional application of pesticides in a vegetable and fruit garden more than doubled (OR 2.29); and, (d) application of pesticides for insects or diseases on outdoor plants by self (OR 1.58) or by professional (OR 1.79).
    [Teitelbaum, S.L., et al. 2007. American Journal of Epidemiology 165(6):643-651.]
  • Pesticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study
    The authors examined the association between pesticide use and breast cancer incidence among farmers’ wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993–1997. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk.
    [Engel, L, Hill, D, Hoppin, J, et al. 2005. Am. J. Epidemiol. 161 (2): 121-135.]
  • Breast cancer and serum organochlorine residues.
    The aim of this study was to compare the blood levels of total dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) in samples collected at the time of breast cancer discovery, in order to avoid the potential consequences of body weight change (after chemotherapy or radiotherapy) on the pesticide residue levels. Blood levels of HCB and total DDT were compared in 159 women with breast cancer and 250 presumably healthy controls. Risk of breast cancer associated with organochlorine concentration was evaluated.Mean levels of total DDT and HCB were significantly higher for breast cancer patients than for controls. No differences in serum levels of total DDT or HCB were found between oestrogen receptor positive and oestrogen receptor negative patients with breast cancer.These results add to the growing evidence that certain persistent pollutants may occur in higher concentrations in blood samples from breast cancer patients than controls.
    [Charlier C, Albert A, Herman P, et al.2003. Occup Environ Med. 60(5):348-51.]
  • Breast cancer risk in Hispanic agricultural workers in California
    A registry-based case control study of breast cancer in farm labor union members in California finds risk of breast cancer to be associated with mushroom crops (OR 6.0) as well as the use of chlordane, malathion, and 2,4-D. According to the study, risk associated with chemical use is stronger in younger women and those with early-onset breast cancer.
    [Mills, P.K. and Yang, R. 2005. Int J Occup Environ Health 11(2):123-131.] Occupational histories of cancer patients in a Canadian cancer treatment center and the generated hypothesis regarding breast cancer and farming
    A Canadian study of newly diagnosed breast cancer patients and woman with other cancers finds that women 55 years and younger who had ever farmed has a significantly increased risk of breast cancer than any other type of occupation.
    [Brophy, J., et al. 2002. International Journal of Occupational and Environmental Health 8(4):346-353.]
  • Mammographic findings and occupational exposure to pesticides currently in use on Crete
    Women occupationally exposed to pesticides in Crete greenhouses have higher risks of incidence for number of breast tissue legions, which are risk markers for subsequent invasive breast cancer.
    [Dolapsakis, G., et al. 2001. Eur J Cancer 37(12):1531-1536.]
  • A population-based case-control study of farming and breast cancer in North Carolina
    A population based, case control study of North Carolina female farmers finds that while farmers in general tend to have lower breast cancer risk, for those women who reported being present in fields during or shortly after a pesticide application (OR 1.8) and for those who reported not using protective clothing while applying pesticides (OR 2.0) are at increased risk for breast cancer.
    [Duell, E.J., et al. 2000. Epidemiology 11(5):523-531.]
  • Identification of occupational cancer risks in British Columbia
    A population based case-control study of breast cancer cases in British Columbia finds excess risk for females in occupations as crop farmers and those in the fruit and vegetable industries.
    [Band, P.R., et al. 2000. J Occup Environ Med 42(3):284-310.]

Cervical Cancer

Colorectal Cancer

  • Use of acetochlor and cancer incidence in the Agricultural Health Study
    Study evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor-exposed cases. Increased risk of lung cancer was observed among acetochlor users compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures, compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users compared to never users. However the lack of exposure-response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.
    [Lerro CC, Koutros S, Andreotti G, Hines CJ, et al. 2015. Int J Cancer.doi: 10.1002/ijc.29416.]
  • Cancer risk among farmers in the Province of Vercelli (Italy) from 2002 to 2005: an ecological study
    Farmers living in the Province of Vercelli (Italy) were observed to verify if they have a higher cancer risk than the rest of the local employed population. The present ecological study considered all cancer new cases recorded among the mean employed population with a range of age from 25 to 84 years and resident in the Province of Vercelli during the four-year period 2002-2005. Farmers showed a higher risk for the following tumors: colorectal (OR 2.38, IC95%: 1,76-2,87), leaukaemia (OR 2.65, IC95%:2,12-2,89), digestive system (OR 2.16, IC95% 1,92-2,33), and others. Farmers showed a higher risk for several cancers. Further studies are needed, in order to examine in detail the issue, to encourage the use of personal protective equipment and to promote a more responsible pesticides use.
    [Salerno C, Sacco S, Panella M, et al.2014. Ann Ig. 26(3):255-63.]
  • A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies.
    The study aimed to systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent "weight-of-evidence" (WOE) methodological approach. Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Only aldicarb and colon cancer and imazethapyr and proximal colon cancer-appears warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose-response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk.
    [Alexander DD, Weed DL, Mink PJ, Mitchell ME. 2012. Int Arch Occup Environ Health. 85(7):715-45.]
  • Lifestyle, occupational, and reproductive factors and risk of colorectal cancer
    Lifestyle factors and environmental exposures might help explain the risk of colorectal carcinoma in countries where the incidence is low, but unique patterns of young onset and a high proportion of rectal cancer exist. Authors obtained detailed lifestyle information from 421 patients with colorectal cancer and 439 hospital-controls in Egypt. A history of pesticide exposure and more frequently eating food directly from farms were significantly associated with a higher risk of colorectal carcinoma (odds ratio = 2.6 and odds ratio = 4.6 respectively). Parous women who reported 7 or more live births or breastfed for 19 months or longer per live birth had a significantly lower risk for colorectal carcinoma. Compared with patients aged 40 years or older, industrial exposures were more common in younger patients. Agricultural and industrial exposures were associated with increased risk of colorectal carcinoma, whereas prolonged lactation and increased parity were inversely associated with colorectal carcinoma in women. Further research to elucidate the biological role of intense environmental and industrial exposures and reproductive factors including lactation may further clarify the etiology of colorectal cancer.
    [Lo AC, Soliman AS, Khaled HM, et al. 2010. Dis Colon Rectum. 53(5):830-7.]
  • Heterocyclic aromatic amine pesticide use and human cancer risk: results form the U.S. Agricultural Health Study
    A prospective cohort study of the Agricultural Health Study evaluated imazethapyr, a heterocyclic aromatic amine herbicide, finding significant trend in risk with increasing lifetime exposure for colon cancer, limited to proximal cancers.
    [Koutros, S., et al. 2009. Int J Cancer 124(5):1206-1212.]
  • Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study
    A study using data from the AHS finds a possible link between trifluralin exposure and colon cancer.
    [Kang, D., et al. 2008. Environ Res 107(2):271-276.]
  • S-Ethyl-N,N-dipropylthiocarbamate exposure and cancer incidence among male pesticide applicators in the Agricultural health Study: A perspective cohort
    An association between the highest category of lifetime the thiocarbamate herbicide EPTC (S-Ethyl-N,N-dipropylthiocarbamate )exposure days and colon cancer is found in participants in the Agricultural Health Study.
    [van Bemmel, D.M., et al. 2008. Environmental Health Perspectives 116(11):1541-1546.]
  • Pesticide use and colorectal cancer risk in the Agricultural Health Study
    A study of agricultural pesticides and colorectal cancer incidence in the Agricultural Health Study, chlorpyrifos shows significant exposure response trend for rectal cancer.
    [Lee, W.J., et al. 2007. Int J Cancer 121(2):339-346.]
  • Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study
    A study using the Agricultural Health Study finds a significant trends of increasing risk for colon cancer for lifetime exposure days and intensity-weighted lifetime days at the highest exposure level.
    [Samanic, C., et al. 2006. Environ Health Perspect 114(10):1521-1526.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk in females for rectum cancer (OR 1.86) and colon cancer (OR 1.65).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]
  • Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States)
    Cancer mortality among farmers shows an excess of deaths for cancers of the rectum (1.29 PMR). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (proportional mortality ratio 1.52) and skin melanoma (proportional mortality ratio 1.60), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (proportional mortality ratio 1.18), lip (proportional mortality ratio 1.58), and leukemia (proportional mortality ratio 1.26).
    [Cerhan, J.R., et al. 1998. Cancer Causes Control 9(3):311-319.]
  • Cancer incidence among Icelandic pesticide users
    Occupational exposure to pesticides in a small Icelandic study shows a significant increased incidence for rectal cancer, especially for licensed pesticide users (standardized incidence ratio 4.63).
    [Zhong, Y. and Rafnsson, V. 1996. International Journal of Epidemiology 25(6):1117-1124.]
  • Proportionate mortality study of golf course superintendents.
    A proportionate mortality study of a cohort of 686 golf course superintendents finds an elevated number deaths from brain cancer (PMR 234), large intestine cancer (PMR 175), NHL (PMR 237), and prostate cancer (PMR 293).
    [Kross, B.C., et al. 1996. Am J Ind Med 29(5):501-506]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a possible relationship between fruit crops and colon and bladder cancer.

    The study also finds a significantly increased risk of rectal cancer among licensed pesticides users with greater than 10 years’ experience.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]

Eye Cancer

  • A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma.
    The risk factors for sporadic (ie, non-familial) retinoblastoma remain largely unknown. Authors examined the relationship between paternal occupational exposures from jobs held 10 years and 1 year prior to conception and the risk of sporadic bilateral retinoblastoma in children.Paternal occupational data were obtained for 198 incident cases diagnosed with sporadic bilateral retinoblastoma from January 1998 to May 2006 and 245 referral-based controls from the case child's relatives and friends who were matched to 135 of the cases on birth year.There was some indication of an elevated risk associated with paternal pesticide exposure in the 10 years prior to conception as well as in the year before conception. However, results for pesticide exposure were inconsistent and varied by analysis approach. Exposure-response trends were observed for pesticides and non-welding metal exposures.Findings suggest a potential role of paternal occupational exposures to non-welding metals and perhaps pesticides in the aetiology of childhood retinoblastoma.
    [Abdolahi A, van Wijngaarden E, McClean MD, et al. 2013. Occup Environ Med. 70(6):372-9]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    Retinoblastoma associated with increased risk estimates for children less than one year of year and up through nine years of age is found in a study looking at children with cancer residence at diagnosis relative to the percent of land used for agriculture in the county.
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    Parental agricultural exposure to pesticides is associated with eye cancer.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]

Gallbladder Cancer

  • Mortality in a cohort of pesticide applicators in an urban setting: sixty years of follow-up
    A cohort study in Rome of urban pesticide applicators finds an increased risk for cancer of the gallbladder, liver, and nervous system.
    [Giordano, F., et al. 2006. Int J Immunopathol Pharmacol 19(Suppl 4):61-65.]
  • Organochlorine pesticides in carcinoma of the gallbladder: a case-control study.
    Carcinoma of the gallbladder is the third most common malignancy of the gastrointestinal tract in the Eastern Uttar Pradesh and Western Bihar regions of India. The main source of drinking water in this region is the river Ganges, which is heavily polluted with agricultural pesticides. Organochlorine pesticides were estimated in bile by gas liquid chromatography in 60 patients (30 carcinoma of the gallbladder and 30 cholelithiasis) to observe its association with aetiopathogenesis of carcinoma of the gallbladder. The mean biliary concentration of benzene hexachloride (BHC) was found to be significantly higher in carcinoma of the gallbladder (0.0471 ppm) than in cholelithiasis (0.0352 ppm) (P < 0.04). The mean biliary concentration of dichlorodiphenyltrichloroethane (DDT) was also significantly higher in carcinoma of the gallbladder (0.418 ppm) than in cholelithiasis (0.0103 ppm) (P < 0.03). Biliary aldrin and endosulfan concentrations were higher in carcinoma of the gallbladder (0.0008 and 0.00132 ppm) than in cholelithiasis (0.0005 and 0.0126 ppm) but the difference was statistically not significant (P < 0.06 and P < 0.9). The levels of pesticides in blood did not show significant differences in either carcinoma of the gallbladder or cholelithiasis. Significantly high biliary BHC and DDT concentrations suggest that these pesticides might be associated with gallbladder carcinogenesi.
    [Shukla VK, Rastogi AN, Adukia TK, et al. 2001. Eur J Cancer Prev. 10(2):153-6.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for gallbladder cancer in males (OR 1.49) and in females (OR 1.73).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]

Kidney/Renal Cancer

  • Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms.
    This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. Study also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles. Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, it was observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.
    [Karami S, Boffetta P, Rothman N, Hung RJ, Stewart T, et al. 2008. Carcinogenesis. 29(8):1567-71]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with moderate to high agriculture activity finds statistically significantly elevated risk for renal carcinoma at moderate agriculture activity (OR 2.3) and at high agriculture activity (OR 3.3). In regards to specific crops grown, the study finds a link between cotton crops and renal carcinomas (OR 6.9).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Wilm’s tumor and exposure to residential and occupational hazardous chemicals
    A case-control study by the CDC finds elevated risk for pesticides during pregnancy and during the 2-year period prior to birth.
    [Tsai, J., et al. 2006. Int J Hyg Environ Health 209(1):57-64.]
  • Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals.
    Study aimed to investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC).One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire. Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals or pesticides. The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null.Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.
    [Buzio L, De Palma G, Mozzoni P, et al. 2003. Occup Environ Med. 60(10):789-93]
  • Occupational risk factors for renal cell cancer. An Italian case-control study.
    “Prolonged” occupational exposures to pesticides is associated with an increased risk for renal cell cancer (OR 2.0).
    [Buzio, L., et al. 2002. Med Lav 93(4):303-309.]
  • Renal cell carcinoma and occupational exposure to chemicals in Canada
    An increased risk of renal cell carcinoma in males is associated with exposure to herbicides (1.6 OR) and pesticides (1.8 OR) and in particular a dose-response relationship for herbicides.
    [Hu, J., et al. 2002. Occup Med 52(3):157-164.]
  • Childhood cancer and paternal employment in agriculture: the role of pesticides
    Paternal occupational exposure to pesticides is statistically significant for kidney cancer, Wilms’ tumor in offspring.
    [Fear, N.T., et al. 1998. Br J Cancer 77(5):825-829.]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    Parental agricultural exposure to pesticides is associated with Wilms’ tumor, as well as other forms of cancer.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
  • Parental exposures to pesticides and risk of Wilms’ tumor in Brazil
    Elevated risk is found for farm work involving paternal (3.24 OR) and maternal (128.6 OR) frequent use of pesticides.
    [Sharpe, C.R., et al. 1995. Am J Epidemiol 141(3):210-217.]
  • Occupational risk factors for renal-cell carcinoma in Denmark
    Risk of renal-cell carcinoma was found to be associated with employment as a truck driver, exposure to gasoline, other hydrocarbons, and insecticides and herbicides. The risk of renal-cell carcinoma was higher in the lower socioeconomic strata for both the men and the women.
    [Mellemgaard, A., et al. 1994. Scand J Work Environ Health 20(3):160-165.]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a significantly increased risk of kidney cancer among farmers with greater than 10 years experience and a possible relationship between olives and potato growing and kidney cancer.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]
  • Risk factors for Wilms tumor
    A study examining nonoccupational risk factors for Wilms tumor finds an association with a history of household insect extermination.
    [Olshan, A.F., et al. 1993. Cancer 72(3):938-944.]

Laryngeal Cancer

  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for larynx cancer in males (OR 1.88).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]
  • Occupational risk factors for cancer of the larynx in Spain.
    Spain is one of the countries with the highest incidence of laryngeal cancer and, together with France, is the country with the lowest percentage of women with this disease. In order to identify the occupational risk factors associated with laryngeal cancer in this country a case-control study was performed. Cases included 85 patients with epidermoid carcinoma of the larynx diagnosed in "La Paz" Hospital, Madrid, between 1985 and 1987. A sample of 170 patients from the same hospital was used as control. The results of the study revealed that 56.5% of larynx cancer patients had a sedentary occupation working in the service sector. Exposure to insecticides or silica were strongest risk factors for laryngeal cancer.
    [Bravo MP, Espinosa J, Calero JR. 1990. Neoplasma. 37(4):477-81.]

Leukemia

Childhood Leukemia

  • Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study.
    This study examined the association of county level agricultural land use and the incidence of specific childhood cancers.Authors linked county-level agricultural census data (2002 and 2007) and cancer incidence data for children ages 0-4 diagnosed between 2004 and 2008 from cancer registries in six Midwestern states. Crop density (percent of county area that was harvested) was estimated for total agricultural land, barley, dry beans, corn, hay, oats, sorghum, soybeans, sugar beets, and wheat. Results found statistically significant exposure-response relationships for dry beans and total leukemias and acute lymphoid leukemias (ALL); oats and acute myeloid leukemias (AML); and sugar beets and total leukemias and ALL. State-level analyses revealed some additional positive associations for total leukemia and CNS tumors and differences among states for several crop density-cancer associations. However, some of these analyses were limited by low crop prevalence and low cancer incidence.The associations observed in this study need to be confirmed by analytic epidemiologic studies using individual level exposure data and accounting for potential confounders that could not be taken into account in this ecologic study.
    [Booth BJ, Ward MH, Turyk ME, Stayner LT. 2015. Environ Health. 14(1):82]
  • Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.
    Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, authors pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39, 1.43 and 1.36, respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49, 1.55 and 1.08, respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias.
    [Bailey HD, Infante-Rivard C, Metayer C, Clavel J, Lightfoot T, et al. 2015. Int J Cancer. 137(11):2644-63.]
  • Household pesticide exposure and the risk of childhood acute leukemia in Shanghai, China.
    Childhood acute leukemia (AL) is the most common malignant tumor in children, but its etiology remains largely unknown. Study investigated the relationship between household exposure to pesticides and childhood AL. Between 2009 and 2010 in Shanghai, a total of 248 newly diagnosed cases of AL and 111 gender-, age-, and hospital-matched controls were included. Five nonspecific dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OPPs) [including dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP)] in the urine were analyzed by gas chromatography. The results showed that the median DMP, DEP, DMTP, DETP, and DEDEP levels adjusted for creatinine (Cr) in cases were all significantly elevated compared with those in controls. The household use of mosquito repellent was significantly associated with an increased risk of childhood AL. Moreover, higher exposures were significantly associated with an elevated risk of childhood AL for DMs, DEs, and DAPs. Findings support the notion that the household use of pesticides may play a role in the etiology of childhood AL and provide some evidence to warrant further investigation of the link between household pesticide exposures and childhood AL in Shanghai.
    [Zhang Y, Gao Y, Shi R, Chen D, Wang X, et al. 2015. Environ Sci Pollut Res Int. 22(15):11755-63.]
  • Relationship between exposure to pesticides and occurrence of acute leukemia in Iran.
    One of the causes of acute leukemia can be exposure to certain chemicals such as pesticides. This study determined the relationship between exposure to pesticides and the occurrence of acute leukemia in Fars province, south of Iran. Between April 2011 and April 2013 in a case-control study conducted in Nemazee Hospital in Shiraz, Southern Iran; 314 subjects diagnosed with acute leukemia (94 pediatric cases and 220 adults) were enrolled to determine any correlation between exposure to pesticides and the occurrence.There was a history of exposure to pesticides among 85% of pediatric cases an d 69% of their controls and 83% of adult cases and 75% of their controls while 87.5% of pediatric cases and 90% of adult cases reported exposure to intermediate and high doses of pesticides and among the controls, the exposure to low doses of pesticides was 70.5% and 65%, respectively. Exposure to indoor pesticides was seen among most of cases and controls. Being a farmer was at a significantly more increased risk of developing acute leukemia in comparison to other jobs, especially for their children. Exposure to pesticides was shown to be one of the most important causes of acute leukemia.
    [Maryam Z, Sajad A, Maral N, Zahra L, et al. 2015. Asian Pac J Cancer Prev. 16(1):239-44.]
  • Residential Exposure to Pesticide During Childhood and Childhood Cancers: A Meta-Analysis.
    In this meta-analysis, authors aimed to examine associations between residential childhood pesticide exposures and childhood cancers.The literature search yielded 277 studies that met inclusion criteria.Sixteen studies were included in the meta-analysis, and authors found that childhood exposure to indoor but not outdoor residential insecticides was associated with a significant increase in risk of childhood leukemia (odds ratio [OR] = 1.47; 95% CI, 1.26-1.72; I(2) = 30%) and childhood lymphomas (OR = 1.43; 95% CI, 1.15-1.78; I(2) = 0%). A significant increase in risk of leukemia was also associated with herbicide exposure (OR = 1.26; 95% CI, 1.10-1.44; I(2) = 0%). Results from this meta-analysis indicated that children exposed to indoor insecticides would have a higher risk of childhood hematopoietic cancers. Additional research is needed to confirm the association between residential indoor pesticide exposures and childhood cancers. Meanwhile, preventive measures should be considered to reduce children's exposure to pesticides at home.
    [Chen M, Chang CH, Tao L, Lu C. 2015. Pediatrics. 136(4):719-29.]
  • Maternal factors and risk of childhood leukemia.
    The aim of this study was to examine association of childhood leukemia with maternal factors especially during pregnancy, to help in avoiding risk factors.This case-control study included children younger than 18 years diagnosed with leukemia from 2008 to 2012. Statistically significant associations between risk of childhood leukemia with mother's education , occupation and pesticides exposure during pregnancy were found. However, there were no significant links with maternal age, history of fetal loss, history of radiography during pregnancy, history of drug intake and infection during pregnancy.The results showed increased risk of leukemia in children whose mothers were working in agriculture and were exposed to pesticides during pregnancy. The further study needs to be investigated to know association of various maternal risk factors with leukemia which remained unknown in this study.
    [Kumar A, Vashist M, Rathee R. 2014. Asian Pac J Cancer Prev. 15(2):781-4.]
  • Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.
    Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. Authors pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 and for paternal exposure around conception 1.20. For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 and for paternal exposure around conception 0.91. Finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. Study also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.
    [Bailey HD, Fritschi L, Infante-Rivard C, Glass DC, et al. 2014. Int J Cancer. 135(9):2157-72.]
  • Exposure to herbicides in house dust and risk of childhood acute lymphoblastic leukemia.
    Study examines the association between exposure to herbicides and childhood acute lymphoblastic leukemia (ALL). Dust samples were collected from homes of 269 ALL cases and 333 healthy controls (<8 years of age at diagnosis/reference date and residing in same home since diagnosis/reference date) in California, using a high-volume surface sampler or household vacuum bags. Amounts of agricultural or professional herbicides (alachlor, metolachlor, bromoxynil, bromoxynil octanoate, pebulate, butylate, prometryn, simazine, ethalfluralin, and pendimethalin) and residential herbicides (cyanazine, trifluralin, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop, 2,4-dichlorophenoxyacetic acid (2,4-D), chlorthal, and dicamba) were measured. The risk of childhood ALL was associated with dust levels of chlorthal; compared to homes with no detections, ORs for the first, second, and third tertiles were 1.49, 1.49, and 1.57, respectively. The magnitude of this association appeared to be higher in the presence of alachlor. No other herbicides were identified as risk factors of childhood ALL. The data suggest that home dust levels of chlorthal, and possibly alachlor, are associated with increased risks of childhood ALL.
    [Metayer C, Colt JS, Buffler PA, Reed HD, et al. 2013. J Expo Sci Environ Epidemiol. 23(4):363-70.]
  • Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in Shanghai.
    Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. This study investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. A hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011 was carried out and included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 1.43-5.29; cis-DCCA: OR = 2.21; trans-DCCA: OR = 2.33; and 3-PBA: OR = 1.84], and most of the positive trends were significant. Findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.
    [Ding G, Shi R, Gao Y, Zhang Y, Kamijima M, et al. 2012. Environ Sci Technol. 46(24):13480-7]
  • Risk of childhood acute lymphoblastic leukaemia following parental occupational exposure to pesticides
    Study was performed to ascertain whether there was an association between parental occupational exposure to pesticides and increased risk of acute lymphoblastic leukaemia (ALL) in the offspring. A population-based case-control study of childhood ALL was conducted in Australia. Information about the occupational pesticide exposure of mothers and fathers was collected using job-specific modules. Information on the types and extent of pesticide exposure was collected for mothers and fathers before and around the time of conception, and also for mothers during pregnancy for the index case or control and for 1 year after birth. Paternal occupational exposure to pesticides before or around conception was not related to increased risk of childhood ALL. There was a low prevalence of occupational exposure to pesticides among women that reduced after birth. Paternal occupational exposure to pesticides was not found to be associated with an increased risk of acute lymphoblastic leukaemia in the offspring. The study was underpowered with respect to maternal exposure to pesticides.
    [Glass DC, Reid A, Bailey HD, et al. 2012. Occup Environ Med. 69(11):846-9.]
  • Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies.
    The authors performed a meta-analysis of case-control and cohort studies to clarify the possible relationship between exposure to pesticides and childhood cancers.Two cohort and 38 case-control studies were selected for the first meta-analysis.Meta-analysis of the three cohort studies did not show any positive links between parental pesticide exposure and childhood cancer incidence. However, the meta-analysis of the 40 studies with OR values showed that the risk of lymphoma and leukaemia increased significantly in exposed children when their mother was exposed during the prenatal period (OR=1.53; 95% CI 1.22 to 1.91 and OR=1.48; 95% CI 1.26 to 1.75). The risk of brain cancer was correlated with paternal exposure either before or after birth (OR=1.49; 95% CI 1.23 to 1.79 and OR=1.66; 95% CI 1.11 to 2.49). The OR of leukaemia and lymphoma was higher when the mother was exposed to pesticides.Despite some limitations in this study, the incidence of childhood cancer does appear to be associated with parental exposure during the prenatal period.
    [Vinson F, Merhi M, Baldi I, Raynal H, Gamet-Payrastre L. 2011. Occup Environ Med. 68(9):694-702.]
  • Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.
    Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs).The ORs for any professional pest control treatments were 1.19 in the year before pregnancy, 1.30 during pregnancy and 1.24 for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. Results provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years.
    [Bailey HD, Armstrong BK, de Klerk NH, et al. 2011. Int J Cancer. 129(7):1678-88]
  • Residential exposures to pesticides and childhood leukemia
    The aim of this study was to conduct a systematic review of published studies on the association between residential/household/domestic exposure to pesticides and childhood leukaemia, and to provide a quantitative estimate of the risk. Publications in English were searched in MEDLINE (1966-31 December 2009) and from the reference list of identified publications. Separate analyses were conducted after stratification for exposure time windows, residential exposure location, biocide category and type of leukaemia. Statistically significant associations with childhood leukaemia were observed when combining all studies. Exposure during and after pregnancy was positively associated with childhood leukaemia, with the strongest risk for exposure during pregnancy. Other stratifications showed the greatest risk estimates for indoor exposure, for exposure to insecticides as well as for acute non-lymphocytic leukaemia (ANLL). Outdoor exposure and exposure of children to herbicides (after pregnancy) were not significantly associated with childhood leukaemia. Findings support the assumption that residential pesticide exposure may be a contributing risk factor for childhood leukaemia but available data were too scarce for causality ascertainment. It may be opportune to consider preventive actions, including educational measures, to decrease the use of pesticides for residential purposes and particularly the use of indoor insecticides during pregnancy.
    [Van Maele-Fabry G, Lantin AC, Hoet P, Lison D. 2011. Environ Int. 37(1):280-91.]
  • Residential pesticides and childhood leukemia: a systematic review and meta-analysis.
    Study is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.
    [Turner MC, Wigle DT, Krewski D. 2011. Cien Saude Colet. 16(3):1915-31.]
  • A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.
    Authors conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.They found no overall association between childhood leukemia and any paternal occupational pesticide exposure; there were slightly elevated risks in subgroups of studies with low total-quality scores, ill-defined exposure time windows, and exposure information collected after offspring leukemia diagnosis. Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51-2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68-3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56-3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53-3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47-5.04) and herbicides (OR = 3.62; 95% CI, 1.28-10.3). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups.
    [Wigle DT, Turner MC, Krewski D. 2009. Environ Health Perspect. 117(10):1505-13]
  • Pediatric acute lymphoblastic leukemia and exposure to pesticides.
    A case-control study of children diagnosed with ALL and their mothers in the Washington DC area finds an association between the development of childhood ALL and common household pesticides, as ALL child-mother pairs have elevated levels for the organophosphate metabolites diethylthiophosphate and diethyldithiophosphate and more case mothers (33%) than controls (14%) reported using insecticides in the home.
    [Soldin, O.P., et al. 2009. Therapeutic Drug Monitoring 31(4):495-501]
  • Residential proximity to agricultural pesticide applications and childhood acute lymphoblastic leukemia
    A population based, case control study in California using residential histories and proximity to agricultural pesticide use shows an elevated risk of childhood ALL associated with moderate exposure, but not high exposure, to pesticides classified as organophosphates, chlorophenoxy herbicides, and triazines, and with agricultural pesticides used as insecticides or fumigants.
    [Rull, R.P., et al. 2009. Environ Res 109(7):891-9]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for AML at high agricultural activity (greater than 60% of county acreage devoted to farming).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Association between prenatal pesticide exposures and the generation of leukemia-associated T(8;21)
    A study analyzing umbilical cord blood samples of infants whose meconium sample detected the pesticide propoxur, finds a two-fold increase incidence of t(8;21)(a22;a22), one of the most common cytogenetic abnormalities in childhood acute myeloid leukemia, suggesting that prenatal pesticide exposure is a factor in the generation of leukemia-associated chromosomal translocations.
    [Lafiura, K.M., et al. 2007. Pediatr Blood Cancer 48(5):624-628]
  • Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE)
    A French registry-based case-control study finds that children born to mothers living in households with pesticide use during pregnancy have over twice as much risk of acute leukemia.
    [Rudant, J., et al. 2007. Environmental Health Perspectives 115(12):1787-1793]
  • Parental occupational exposure to pesticides and the risk of childhood leukemia in Costa Rica.
    In a Costa Rica population-based, case-control study, researchers find parental occupational exposure to pesticides increases the risk of childhood leukemia. Maternal pesticide exposure doubles offspring leukemia risk, whether before conception (OR 2.4), or during the first (OR 22) or second trimesters (OR 4.5) the risk is significant. Paternal pesticide exposure during the second trimester also increases risk (1.5 OR) in offspring. In regards to organophosphates, maternal exposure during the first trimester is three and a half times higher (OR 3.5). Exposure to benzimidazole pesticides during pregnancy also has twice the risk for childhood leukemia (OR 2.2)
    [Monge, P., et al. 2007. Scandinavian Journal of Work, Environment and Health 33(4):293-303]
  • Child and maternal household chemical exposure and the risk of acute leukemia in children with Down's syndrome: a report from the Children's Oncology Group
    Children with Down’s syndrome have about a 20-fold increased risk for developing leukemia. A case-control study of acute leukemia in children with Down’s syndrome finds a positive association for acute lymphoblastic leukemia and maternal exposure to professional pest exterminations and to any pesticide.
    [Alderton, L.E., et al. 2006. American Journal of Epidemiology 164(3):212-221]
  • Household exposure to pesticides and risk of childhood acute leukaemia
    A study of household pesticide exposure and childhood acute leukemia finds an increased risk for maternal home insecticide use during pregnancy and during childhood, and with garden insecticide use and fungicide use during childhood. Pyrethroid and lindane lice shampoo treatment is also associated with childhood acute leukemia. The majority of the childhood cancers were acute lymphocytic leukemia.
    [Menegaux, F., et al. 2006. Occup Environ Med 63(2):131-134]
  • Agricultural pesticide use and childhood cancer in California.
    Looking at residential proximity to agricultural pesticides, a population-based case-control study of early childhood cancer, ages 0-4 years, in California finds an elevated risk for leukemia associated with probable and possible carcinogen use and with nearby agricultural applications of organochlorines and organophosphates during pregnancy (metam sodium OR 2.05 and dicofol OR 1.83)
    [Reynolds, P, et al. 2005. Epidemiology 16(1):93-100]
  • Critical windows of exposure to household pesticides and risk of childhood leukemia.
    A case-control study in California finds a significant increased risk of childhood leukemia to the use of professional indoor pesticide applications at any time from one year before birth to three years after. In addition, frequency of exposure to pesticides was also linked with increased risk
    [Ma, X., et al. 2002. Critical windows of exposure to household pesticides and risk of childhood leukemia. Environmental Health Perspectives 110:955-960]
  • Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion
    A small case-control, population-based study finds a significant increase risk for infant acute leukemia for maternal exposure to insecticides (OR 9.68) during pregnancy, including the carbamate propoxur.
    [Alexander, F.E., et al. 2001. Cancer Res 61(6):2542-2546]
  • Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms.
    A population-based case-control study of childhood ALL finds an increased risk for homeowner use of indoor insecticides and garden and interior plant pesticides, in particular with use during pregnancy and among carriers of the CYP1A1m1 and CYP1a1m2 gene mutations.
    [Infante-Rivard, C., et al. 1999. Epidemiology 10(5):481-487]
  • Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany
    A population-based case-control study in Northern Germany finds a significant association for pesticide use in gardens and childhood leukemia.
    [Meinert, E., et al. 1996. Eur J Cancer32A(11):1943-1948]
  • Home pesticide use and childhood cancer: A case-control study
    A case-control study in Denver finds home use of pest strips containing dichlorvos is linked to childhood leukemia. The highest risk is found for exposure during the last 3 months of pregnancy, for exposure during the 2 years prior to diagnosis, and for exposure from birth through 2 years prior to diagnosis.
    [Leiss, J., et al. 1995. American Journal of Public Health 85:249-252]
  • Case-control study on the association between a cluster of childhood haematopoietic malignancies and local environmental factors in Aalsmeer, The Netherlands.
    A small case-control study of a flower cultivation community in the Netherlands finds an increase risk for childhood hematopoietic malignancies, such as leukemia, for parental occupational use of pesticides.
    [Mulder, Y.M., et al. 1994. Journal of Epidemiology and Community Health 48:161-165]
  • Epidemiological characteristics of childhood acute lymphocytic leukemia. Analysis by immunophenotype. The Childrens Cancer Group.
    A California study shows children’s exposure to insecticides is associated with a five-fold increase in childhood ALL.
    [Buckley, J.D., et al. 1994. Leukemia 8(5):856-864]
  • Parental occupation and other environmental factors in the etiology of leukemias and non-Hodgkin's lymphomas in childhood: a case-control study
    A hospital-based case-control study in Italy finds a positive association with paternal work as a farmer and childhood ALL
    [Magnani, C., et al. 1990. Tumori 76(5):413-419]
  • Occupational Exposures of Parents of Children with Acute Nonlymphocytic Leukemia: A Report from the Childrens Cancer Study Group
    A case-control study finds a consistent pattern of association of AML, also known as acute nonlymphoblastic leukemia (ANLL), risk with paternal exposure to pesticides for jobs held longer than three years, which is substantially increased for children under age 6 at diagnosis. An elevated risk is also found for a child’s direct exposure to pesticides in the home and for maternal exposure to home pesticides at the time of pregnancy.
    [Buckley, J.D., et al. 1989. Cancer Research 49:4030-4037]
  • A population-based case-control study of childhood leukemia in Shanghai
    A population based case-control study in China of childhood leukemia cases finds an association between ALL with maternal occupational exposure to pesticides.
    [Shu, X.O., et al. 1988. Cancer 62(3):635-644]
  • Environmental factors in childhood leukaemia.
    A small French case-control study finds paternal occupational exposures to pesticides as a risk factor for leukemia (12 cases versus 3 controls)
    [Laval, G. and Tuyns, A.J. 1988. British Journal of Industrial Medicine 45:843-844]
  • Childhood leukemia and parents' occupational and home exposures.
    A case-control study in California finds household pesticide use can more than triple the risk of childhood leukemia and that garden pesticides increase the risk to over six-fold.
    [Lowengart, R., et al. 1987. Journal of the National Cancer Institute 79(1):39-46]

Adult Leukemia

Lip Cancer

  • Pesticide sales and adult male cancer mortality in Brazil.
    A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.
    [Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]
  • Cancer incidence among farmers exposed to lindane while sheep dipping
    The objective of this study was to determine whether site-specific cancer incidence among farmers exposed to the insecticide lindane (g-hexachlorocyclohexane) while dipping sheep differs from that of the general population in Iceland.Cohorts of 7882 men and 429 women, who, according to records on sheep dipping, were sheep owners, were followed from 1962 to 2003 in the Cancer Registry for cancer incidence.For men the standardized incidence ratio (SIR) for all cancer sites was 0.79, with a 95% confidence interval (95% CI) of 0.76-0.83. For both the men and the women a significantly increased risk for lip cancer was found, with SIR of 1.50 (95% CI 1.08-2.04) and 9.09 (95% CI 1.02-32.82), respectively. Cancer of the lip was the only cancer type in significant excess among both genders, and the stomach cancer rates were near unity, but, in previous studies on Icelandic farmers, an increase had been found for stomach cancer. The site-specific cancer incidence for sheep-dipping farmers did not differ substantially from that of the general population.
    [Rafnsson V. 2006. Scand J Work Environ Health. 32(3):185-9.]
  • Incidence of lip cancer in the male Norwegian agricultural population
    Study explored lip cancer (LC) associations with work environmental exposures in a record-linkage study of Norwegian farmers. A cohort of 131,243 male Norwegian farmers born 1925-1971 was established by cross-linkage of national registers and followed up through 1999 for incident LC, (ICD-7 site 140) in the Cancer Registry of Norway. Study identified 108 LC cases (rate 4.4 per 100,000 person-years) and found LC to be moderately associated with horses on the farm (RR = 1.6, CI = 1.0-2.4), construction work employment (RR = 1.7, CI = 1.1-2.6), pesticide use (RR = 0.7, CI = 0.4-1.0), grain production (RR = 1.3, CI = 0.9-2.1) and increasing levels of fungal forecasts (RR = 1.6, CI = 0.9-2.8 in the highest two quartiles).Moderate associations of LC with grain production and fungal forecasts and the negative association with pesticide could possibly be explained by exposure to immunosuppressive mycotoxins. Some of the associations observed could be explained by solar exposure.
    [Nordby KC, Andersen A, Kristensen P. 2004. Cancer Causes Control. 15(6):619-26.]
  • Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States)
    Cancer mortality among farmers shows an excess of deaths for cancers of the rectum (1.29 PMR). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (proportional mortality ratio 1.52) and skin melanoma (proportional mortality ratio 1.60), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (proportional mortality ratio 1.18), lip (proportional mortality ratio 1.58), and leukemia (proportional mortality ratio 1.26).
    [Cerhan, J.R., et al. 1998. Cancer Causes Control 9(3):311-319.]
  • Swedish agricultural workers: A group with a decreased risk of cancer
    A Swedish study based on a cancer registry of agricultural workers finds an increased risk of cancer of the lip by a factor of greater than 2.
    [Wiklund, K. 1983. Cancer 51(3):566-568.]

Liver/Hepatic Tumors

  • Mode of action analysis for pesticide-induced rodent liver tumours involving activation of the constitutive androstane receptor: relevance to human cancer risk.
    A number of non-genotoxic chemicals, including some pesticides, have been shown to increase the incidence of liver tumours in rats and/or mice. Frameworks for analysing the modes of action (MOAs) by which chemicals produce liver tumours in rodents and the relevance of such tumour data for human risk assessment have now been established. One common MOA for rodent liver tumour formation by non-genotoxic chemicals involves activation of the constitutive androstane receptor (CAR). Key and associative events for a CAR-activation MOA include receptor activation, liver hypertrophy, induction of cytochrome P450 enzyme activities, increased replicative DNA synthesis, altered hepatic foci and liver tumours. While some effects of rodent CAR activators can be observed in human liver, a major species difference is that, unlike rodents, CAR activators do not increase replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent liver tumour formation is thus not plausible for humans, and hence such compounds do not pose a hepatocarcinogenic hazard for humans.
    [Lake BG, Price RJ, Osimitz TG. 2015.Pest Manag Sci.71(6):829-34]
  • Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data.
    Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. Study aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS).Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53kg/km2 of organochlorine pesticides (75th percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76), but not associated with HCC among females (adjusted OR 0.83).This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females.
    [VoPham T, Brooks MM, Yuan JM, Talbott EO, et al. 2015. Environ Res.143(Pt A):68-82.]
  • Evaluation of hepatotoxicity and clastogenicity of carbofuran in male Wistar rats.
    The present study examined the hepatotoxicity and clastogenic effects of carbofuran in rats. Male Wistar rats were exposed to carbofuran (p.o) at 0-5mg/kg bw for 5weeks. Carbofuran induced significant increase in the serum activity of gamma-glutamyltransferase when compared with the negative control, but not activity of serum alanine and aspartate aminotransferases. It also significantly induced micronucleated polychromatic erythrocytes formation in the bone marrow as compared with the control. The level of induction is dose dependent in both cases. In addition, there was significant higher number of hepatic cells in the cell/mm(2) assay for the group treated with carbofuran. Findings from this study suggest that carbofuran has clastogenic and hepatotoxic effects in rats. It therefore may constitute an environmental health risks in individuals so exposed.
    [Gbadegesin MA, Owumi SE, Akinseye V, Odunola OA. 2014. Food Chem Toxicol. 65:115-9.]
  • Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG cells.
    In the present study, cytotoxicity and genotoxicity of malathion and isomalathion either individually or in combination, were assessed using the metabolically competent human liver HepaRG cell line. Isomalathion reduced cell viability starting at a 100 μM concentration after a 24h exposure. It also significantly induced caspase-3 activity in a dose-dependent manner starting at 5 μM. Co-exposure of both compounds resulted in decreased toxicity of isomalathion. By contrast, malathion and isomalathion either separately or in combination, slightly induced micronuclei formation at low concentrations and had additive genotoxic effects when combined at 25 μM. Individually or combined isomalathion directly inhibited activity of carboxyesterases which are involved in detoxication of malathion. Results showed that isomalathion was much more cytotoxic than malathion while both compounds had comparable genotoxic effects in HepaRG hepatocytes at low concentrations and brought further support to the importance of considering impurities and interactions during evaluation of health risks of pesticides.
    [Josse R, Sharanek A, Savary CC, Guillouzo A. 2014. Chem Biol Interact. 209:68-76]
  • Potential involvement of chemicals in liver cancer progression: an alternative toxicological approach combining biomarkers and innovative technologies.
    In order to evaluate the in vitro effects of chemicals present in the diet, study began by combining viability, real-time cellular impedance and high throughput screening data to identify a concentration "zone of interest" for the six xenobiotics selected: endosulfan, dioxin, carbaryl, carbendazim, p'p'DDE and hydroquinone. Study identified a single concentration of each pollutant allowing a modulation of the impedance in the absence of vital changes (nuclear integrity, mitochondrial membrane potential, cell death). Based on the number of observed modulations known to be involved in hepatic homeostasis dysfunction that may lead to cancer progression such as cell cycle and apoptosis regulators, EMT biomarkers and signal transduction pathways, authors then ranked the pollutants in terms of their toxicity. Endosulfan, was able to strongly modulate all the studied cellular processes in HepG2 cells, followed by dioxin, then carbendazim. Results of in vitro data indicate that these xenobiotics may contribute to the evolution and worsening of hepatocarcinoma.
    [Peyre L, Zucchini-Pascal N, de Sousa G, et al. 2014. Toxicol In Vitro. 28(8):1507-20.]
  • Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a two-stage hepatocarcinogenesis model.
    To identify key molecules in piperonyl butoxide (PBO)-induced hepatocarcinogenesis, study searched hypermethylated genes using CpG island (CGI) microarrays in non-neoplastic liver cells as a source of proliferative lesions at 25 weeks after tumor promotion with PBO using mice. The study further performed methylation-specific polymerase chain reaction (PCR), real-time reverse transcription PCR, and immunohistochemical analysis in PBO-promoted liver tissues. Ebp4.1, Wdr6 and Cmtm6 increased methylation levels in the promoter region by PBO promotion, although Cmtm6 levels were statistically non-significant.Results suggest that PBO promotion may cause altered epigenetic gene regulation in non-neoplastic liver cells surrounding proliferative lesions to allow the facilitation of hepatocarcinogenesis. Both Wdr6 and Cmtm6 showed decreased expression in non-neoplastic liver cells in contrast to positive immunoreactivity in the majority of proliferative lesions produced by PBO promotion. These results suggest that both Wdr6 and Cmtm6 were spared from epigenetic gene modification in proliferative lesions by PBO promotion in contrast to the hypermethylation-mediated downregulation in surrounding liver cells. Considering the effective detection of proliferative lesions, these molecules could be used as detection markers of hepatocellular proliferative lesions and played an important role in hepatocarcinogenesis.
    [Yafune A, Kawai M, Itahashi M, et al. 2013. Toxicol Lett. 222(3):295-302]
  • Risk of hepatocellular carcinoma in workers exposed to chemicals
    In this study, a review of the literature found that while laboratory data clearly indicate that the liver is an important target of chemical carcinogenesis, epidemiological studies provide very limited evidence on occupational risk factors for HCC. Nevertheless, study found some case reports and epidemiological data showing a moderately increased risk of HCC development in people exposed to vinyl chloride, organic solvents, pesticides, polychlorinated biphenyls, and arsenic. Occupational exposure to chemicals may be another risk factor for HCC development, but the interpretation of currently available findings is limited by the small number of studies, questionable accuracy of the diagnosis of liver cancer, and potential confounding or modifying factors such as chronic hepatitis virus infection and alcohol consumption. Further relevant investigations are required for clarifying the actual contribution of occupational exposure to chemicals in HCC development.
    [Uccello M, Malaguarnera G, Corriere T, et al. 2012. Hepat Mon. 12(10 HCC):e5943.]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for hepatic tumors (OR 3.3) and for subtype hepatoblastoma (OR 4.0) at high agricultural activity (greater than 60% of county acreage devoted to farming).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Mortality in a cohort of pesticide applicators in an urban setting: sixty years of follow-up
    A cohort study in Rome of urban pesticide applicators finds an increased risk for cancer of the gallbladder, liver, and nervous system.
    [Giordano, F., et al. 2006. Int J Immunopathol Pharmacol 19(Suppl 4):61-65.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with a two-fold increase risk for liver cancer in females (OR 2.20).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]

Lung Cancer

  • Chronic exposure to chlorophenol related compounds in the pesticide production workplace and lung cancer: a meta-analysis.
    Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. Study is a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer.Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9).Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).
    [Zendehdel R, Tayefeh-Rahimian R, Kabir A. 2014. Asian Pac J Cancer Prev. 15(13):5149-53.]
  • Risk factors for lung cancer in the Pakistani population.
    In this retrospective case-control study, 400 cases and 800 controls were enrolled from different hospitals of all provinces of Pakistan. Information about socio-demographic, occupational, lifestyle and dietary variables was extracted by questionnaire from all subjects. Strong associations were observed for smoking (OR=9.4), pesticide exposure (OR=5.1), exposure to diesel exhaust (OR=3.1). Other associated factors observed were family history (OR=2.0) wood dust (OR=1.9), asbestos exposure(OR=1.5). Strongest dose-response relationships were observed for smoking , pesticide exposure and exposure to diesel exhaust.
    [Luqman M, Javed MM, Daud S, Raheem N, et al. 2014. Asian Pac J Cancer Prev. 15(7):3035-9.]
  • TP53 gene mutations of lung cancer patients inupper northern Thailand and environmental risk factors
    A study that evaluated the risk factors that influence TP53 gene mutation (which is observed in about 40-70% of lung cancer tissues) in lung cancer patients finds that these mutations are induced by exposure to substances other than tocacoo smoke, possibly pesticide exposure.
    [Bumroongkit, K., et al. 2008. Cancer Genet Cytogenet 185(1):20-27.]
  • Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study
    An Agricultural Health study finds for low-exposed pesticide applicators, a positive trend in risk between lifetime exposure days and lung cancer.
    [Samanic, C., et al. 2006. Environ Health Perspect 114(10):1521-1526.]
  • Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study
    Using the Agricultural Health Study, a prospective cohort suty of licensed pesticide applicators in North Carolina and Iowa, finds a nonsignificant increased risk for lung cancer with lifetime days exposure in the highest category (RR 2.37).
    [Rusiecki, J.A., et al. 2006. Int J Cancer 118(12):3118-3123.]
  • Cancer incidence among male pesticide applicators in the Agricultural Health Study cohort exposed to diazinon
    Using the Agricultural Health Study cohort, an association is found for lifetime exposure days to diazinon and cases of leukemia and lung cancer.
    [Beane Freeman, L.E., et al. 2005. American Journal of Epidemiology 162(11):1070-1079]
  • Parental occupational exposures and Ewing’s sarcoma
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with a twofold increase risk for lung cancer for both males and females (OR 2.01 males; 2.63 females).
    [Moore, L.E., et al. 2005. Int J Cancer 114(3):472-478.]
  • Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study
    The rate of lung cancer increases among those workers with higher levels of chlorpyrifos exposure. Individuals in the highest quartile of lifetime exposure-days had more than twice the risk of lung cancer compared with those with no chlorpyrifos exposure. Even when study authors controlled for other factors such as smoking, family history of cancer, and age, the chlorpyrifos link to lung cancer remained.
    [Lee WJ, et al. 2004. J Natl Cancer Inst. 96(23):1781-9.]
  • Pesticides and lung cancer risk in the Agricultural Health Study Cohort
    Four agricultural pesticides are associated with a significant excess lung cancer risk in the Agricultural Health Study cohort.
    [Alavanja, M.C.R., et al. 2004. American Journal of Epidemiology 160(9):876-885.]
  • Cohort mortality and nested case-control study of lung cancer among structural pest control workers in Florida (United States)
    Lung cancer risk is greater for structural pest control workers than non-pest control workers, significant findings include if the worker was first licensed before age 40 (OR 2.4) and for workers licensed 20 or more years (OR 2.1).
    [Pesatori, A.C., et al. 1994. Cancer Causes and Control 5:310-318.]
  • Occupational risk factors for lung cancer among nonsmoking women: a case-control study in Missouri (United States)
    A population-based, case-control study of nonsmokers finds elevated risk among women exposed to pesticides (OR 2.4) for lung cancer.
    [Brownson, R.C., et al. 1993. Cancer Causes Control 4(5):449-454.]
  • Lung cancer and other causes of death among licensed pesticide applicators.
    A cohort study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to lung cancer. Although individuals’ tobacco use was not available, a 1983 study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to cancer of the lungs and that the risk increased with the number of years licensed. Mortality is shown to be greatest for those first licensed before age 40 than among those individuals licensed after age 40.
    [Blair, A., et al. 1983. J Natl Cancer Inst 71(1):31-37]
  • Increased risk of lung cancer in pesticide-exposed male agricultural workers
    A 1981 study of male German agricultural workers exposed to pesticides finds a dose-effect relationship between duration of employment and lung cancer mortality.
    [Barthel, E. 1981. J Toxicol Environ Health 8(5-6):1027-1040.]

Lymphoma

Hodgkin's Lymphoma

  • Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.
    Study's aim was to determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens.
    [Navaranjan G, Hohenadel K, Blair A, Demers PA, et al. 2013. Cancer Causes Control. 24(9):1661-73]
  • Hodgkin lymphoma and pesticides exposure in men: a Canadian case-control study.
    The objective of this study was to investigate the putative associations of specific pesticides with Hodgkin lymphoma. A population-based, case-control study of Hodgkin lymphoma was conducted among males in six regions of Canada. Comparisons of 316 Hodgkin lymphoma cases and 1506 controls identified several factors as predictors for increased Hodgkin lymphoma risk: family history of cancer, exposure to the insecticide chlorpyrifos [OR (95% CI) = 1.19 (1.03, 1.37)], and previous diagnosis of acne or shingles. The increased risk of developing Hodgkin lymphoma detected among Canadian men who used chlorpyrifos must be interpreted cautiously; however the strength of its association indicates that it requires investigation in other populations.
    [Karunanayake CP, Spinelli JJ, McLaughlin JR, et al. 2012. J Agromedicine. 17(1):30-9.]
  • Ethnicity and incidence of Hodgkin lymphoma in Canadian population
    Research has shown that ethnicity is a significant predictor of Hodgkin lymphoma (HL). Other risk factors important in the etiology of HL are medical history and exposure to pesticides. In this report authors investigated the association between ethnicity and HL in the presence of medical history, and exposure to pesticides.In the study population, the distribution of ethnic groups was: 38.5% North American, 15% British, 8.4% Western European, 8.2% Eastern European, 1.7% Asian, 1.4% Scandinavian and 27% of other ethnic origin. Compared to North Americans (i) the risk of HL was greater among the Eastern European descendents (Odds Ratio (ORadj): 1.82) and Western European (ORadj: 1.62) descent population; and (ii) the risk of HL was lower in Asian descents. Exposure to individual herbicide dichlorprop showed an increased risk of HL (ORadj: 6.35).
    [Pahwa P, Karunanayake CP, Spinelli JJ, et al. 2009. BMC Cancer. 9:141]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE)
    A 2007 case-control study in France finds that the mothers use of any household pesticide use is associated with mixed-cell Hodgkin lymphoma (HL).
    [Rudant, J., et al. 2007. Environmental Health Perspectives 115(12):1787-1793]
  • Occupation and lymphoid malignancies: results from a French case-control study
    A multicentered hospital based case-control study in France finds that self-declared occupational pesticide exposure is significantly associated with HL
    [Orsi, L, et al. 2007. J Occup Environ Med 49(12):1339-1350]
  • Exposure to non-arsenic pesticides is associated with lymphoma among farmers in Spain
    A case-control study in Spain finds that crop and animal farmers exposed to non-arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran) have an increased risk of lymphoma (OR 2.8).
    [van Balen, E., et al. 2006. Occupational and Environmental Medicine 63:663-668]
  • Cancer risk and parental pesticide application in children of Agricultural Health Study participants.
    A perspective study of Iowa and North Carolinian children of farmers using pesticides show a greater than two-fold increased risk of childhood lymphoma compared with the general population .
    [Flower, K., et al. 2004. Environmental Health Perspectives 112:631-635]
  • Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States)
    A cancer mortality study of Iowa farmers shows an excess of deaths for Hodgkin's disease.
    [Cerhan, J.R., et al. 1998. Cancer Causes Control 9(3):311-319.]
  • Some occupational exposures as risk factors for malignant lymphomas.
    A Swedish case-referent occupational exposure study finds a significant risk for Hodgkin lymphoma (OR 7.4) for workers exposed to phenoxy herbicides
    [Persson, B., et al. 1993. Cancer 72(5):1773-1778]

Non-Hodgkin's Lymphoma

  • Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study.
    A population based case-control occupational study of Swedish males with hairy cell leukemia find that exposure to herbicides (OR 2.9), insecticides (OR 2.0), fungicides (OR 3.8) and impregnating agents (OR 2.4) shows increased risk.
    [Nordstrom, M., et al. 1998. Br J Cancer 77(11):2048-2052.]
  • Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study.
    There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals. Study determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk.A population-based case-control study of NHL in four National Cancer Institute-Surveillance, Epidemiology, and End Results centers-Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington-from 1998 to 2000 was conducted. The WQS index was statistically significantly associated with NHL overall and in the study sites of Detroit, Los Angeles, and Iowa. The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. An index of chemical mixtures was significantly associated with NHL. Results show the importance of evaluating chemical mixtures when studying cancer risk.
    [Czarnota J, Gennings C, Colt JS, De Roos AJ, et al. 2015. Environ Health Perspect. 123(10):965-70]
  • Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.
    In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL. Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL. Insecticide exposures may contribute to risk of CLL/SLL and DLBCL.
    [Schinasi LH, De Roos AJ, Ray RM, Edlefsen KL, et al. 2015. Ann Epidemiol. 25(11):803-810.e4]
  • Soft tissue sarcoma, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia in workers exposed to phenoxy herbicides: extended follow-up of a UK cohort.
    Study aimed to provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). Authors extended follow-up to December 2012 for 8036 men employed at five factories in the UK which had manufactured phenoxy herbicides, or in a contract spraying business. Mortality from all causes and all cancers was close to expectation, but an excess of deaths from NHL was observed among men who had worked for ≥1 year in jobs with more than background exposure to phenoxy herbicides (19 deaths, SMR 1.85, 95% CI 1.12 to 2.89). Four deaths from STS occurred among men potentially exposed above background (3.3 expected). Findings are consistent with the current balance of epidemiological evidence. If phenoxy herbicides pose a hazard of either STS or NHL, then any absolute increase in risk is likely to be small.
    [Coggon D, Ntani G, Harris EC, et al. 2015. Occup Environ Med.72(6):435-41.]
  • Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.
    This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.
    [Schinasi L, Leon ME. 2014. Int J Environ Res Public Health. 11(4):4449-527.]
  • Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.
    Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Study evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.
    [Alavanja MC, Hofmann JN, Lynch CF, Hines CJ, et al. 2014. PLoS One. 9(10):e109332]
  • Case-control study of risk factors for Non-Hodgkin lymphoma in Mumbai, India.
    In India, among males, NHL incidence rates vary across the country which has encouraged us to conduct a case-control study to study risk factors.The present unmatched hospital-based case-control study conducted at Tata Memorial Hospital included subjects registered between the years 1997-99. There were 390 'lymphoma cases' and 1,383 'normal controls. Among occupational exposure, exposure to use of pesticides showed 3-fold excess risk for lymphoma.
    [Balasubramaniam G, Saoba S, Sarade M, Pinjare S. 2013. Asian Pac J Cancer Prev. 14(2):775-80.]
  • Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.
    Study's aim was to determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens.
    [Navaranjan G, Hohenadel K, Blair A, Demers PA, et al. 2013. Cancer Causes Control. 24(9):1661-73]
  • Hypospadias and residential proximity to pesticide applications.
    Examine the association of hypospadias with residential proximity to commercial agricultural pesticide applications.The study population included male infants born from 1991 to 2004 to mothers residing in 8 California counties. Cases (n = 690) were ascertained by the California Birth Defects Monitoring Program; controls were selected randomly from the birth population (n = 2195). Authors determined early pregnancy exposure to pesticide applications within a 500-m radius of mother's residential address, using detailed data on applications and land use. Forty-one percent of cases and controls were classified as exposed to 57 chemical groups and 292 chemicals. Despite >500 statistical comparisons, there were few elevated odds ratios with confidence intervals that excluded 1 for chemical groups or specific chemicals. Those that did were for monochlorophenoxy acid or ester herbicides; the insecticides aldicarb, dimethoate, phorate, and petroleum oils; and adjuvant polyoxyethylene sorbitol among all cases; 2,6-dinitroaniline herbicides, the herbicide oxyfluorfen, and the fungicide copper sulfate among mild cases; and chloroacetanilide herbicides, polyalkyloxy compounds used as adjuvants, the insecticides aldicarb and acephate, and the adjuvant nonyl-phenoxy-poly(ethylene oxy)ethanol among moderate and severe cases. Odds ratios ranged from 1.9 to 2.9.Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations.
    [Carmichael SL, Yang W, Roberts EM, et al. 2013. Pediatrics. 132(5):e1216-26]
  • Non-Hodgkin lymphoma and pesticide exposure in Turkey.
    The study used data from 1995 to 2010 on the patients who were histopathologically diagnosed with NHL during these years. An increase in the NHL incidence over the years was identified, with a 2.42-fold increment found from 1995 to 2005 and a 2.77 fold elevation from 1995 to 2010. The use of pesticides increased 1.89 fold over the same period.Study investigated the relationship of the pesticides used with NHL patients diagnosed during the same year. Since the time elapsing after exposure to pesticides until the development of cancer is not clear, no comparison can be made at present. We believe that the increase in use of pesticides since 1995 may be associated with the increase in the incidence of NHL and therefore that further studies on the issue including measurements of serum pesticide levels, are required.
    [Yildirim M, Karakilinc H, Yildiz M, Kurtoglu E, et al. 2013. Asian Pac J Cancer Prev. 14(6):3461-3.]
  • Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada.
    The objective was to examine the association between non-Hodgkin's lymphoma (NHL) and farming-related activities, gender, pesticides exposure, and exposure to chemicals other than pesticides in Saskatchewan. Male and female study participants were taken from two separate case-control studies conducted in Saskatchewan province, Canada. A case was defined as any man or woman aged 19 years and older with a first diagnosis of NHL registered by the Saskatchewan Cancer Agency during the study period. Farming exposure and exposure to pesticides-contaminated cloths were related to an increased risk of NHL. Exposure to pesticides was strongly associated with an increased risk of NHL, especially for men.
    [Karunanayake CP, Dosman JA, Pahwa P. 2013. Indian J Occup Environ Med.17(3):114-21]
  • Pesticide use and non-Hodgkin's lymphoma mortality in Brazil.
    Brazil is one of the major pesticide consumers in the world. The continuous exposure to these substances may be etiologically associated with the development of Non-Hodgkin's Lymphoma (NHL). Study's goal was to Estimate the correlation between the per capita sales of pesticides in 1985 (exposure) and NHL mortality rates between 1996 and 2005 (outcome), by Brazilian micro-regions. A moderate correlation between per capita pesticides consumption and standardized mortality rate for NHL was observed (r=0.597). In addition, using the lowest quartile of pesticide consumption as a reference, the higher the quartile of pesticide consumption, the higher was NHL mortality risk: men - (second quartile - MRR=1.69, CI 95% 1.68-1.84; third quartile - MRR=2.41, CI 95% 2.27-2.57; fourth quartile - MRR=2.92, CI 95% 2.74-3.11) and females (second quartile - MRR=1.87, CI 95% 1.69-2.06; third quartile - MRR=2.28, IC 95% 2.10-2.47; fourth quartile - MRR=3.20; CI 95% 2.98-3.43).Results suggest that pesticide exposure may play a role in the etiology of NHL.
    [Boccolini Pde M, Boccolini CS, Chrisman Jde R, et al. 2013. Int J Hyg Environ Health. 216(4):461-6.]
  • A prospective study of organochlorines in adipose tissue and risk of non‑Hodgkin lymphoma.
    Purpose here was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL.Authors conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997 and measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Results found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.
    [Bräuner EV, Sørensen M, Gaudreau E, LeBlanc A, et al. 2012. Environ Health Perspect.120(1):105-11.]
  • Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces.
    Pesticide exposures and immune suppression have been independently associated with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case-control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67) compared to subjects without any of these conditions (OR = 0.81). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25) versus subjects with none of these conditions (OR = 2.44). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results.
    [Pahwa M, Harris SA, Hohenadel K, McLaughlin JR, et al.2012.Int J Cancer. 131(11):2650-9.]
  • Increased risk of non-Hodgkin lymphoma and serum organochlorine concentrations among neighbors of a municipal solid waste incinerator.
    Study investigated organochlorines and the risk of NHL among neighbors of a French MSWI with high levels of dioxin emissions (Besançon, France), using serum concentrations to assess exposure. Risks of NHL associated with each lipid-corrected serum concentration were estimated using exact logistic regression. The pesticides β-hexachlorocyclohexane (odds ratio [OR]=1.05, 95% confidence interval [CI]=1.00-1.12, per 10 ng/g lipid) and p,p' dichloro-diphenyl-trichloroethane (DDT) (OR=1.20, 95% CI=1.01-1.45, per 10 ng/g lipid) were associated with NHL risk. Evidence indicated an increased NHL risk associated with cumulative WHO(1998)-toxic equivalency factor (TEQ) concentrations (dioxins, OR=1.12, 95% CI=1.03-1.26; furans, OR=1.16, 95% CI=1.03-1.35; dioxin-like PCBs, OR=1.04, 95% CI=1.00-1.07; and total TEQ, OR=1.04, 95% CI=1.01-1.05), as well as with non dioxin-like PCBs (OR=1.02, 95% CI=1.01-1.05, per 10 ng/g lipid). Most congener-specific associations were statistically significant. This study provides strong and consistent support for an association between serum cumulative WHO(1998)-TEQ concentrations, at levels experienced by people residing in the vicinity of a polluting MSWI, and risk of NHL.
    [Viel JF, Floret N, Deconinck E, Focant JF, et al. 2011. Environ Int. 37(2):449-53.]
  • Mortality of US pentachlorophenol production workers through 2005.
    A cohort of 2122 US pentachlorophenol (PCP) production workers from four plants in the National Institute for Occupational Safety and Health Dioxin Registry was exposed to PCP and to polychlorinated dibenzo-p-dioxin and dibenzofuran contaminants of PCP production. A subcohort of 720 was also exposed to 2,3,7,8-tetrachlorodibenzodioxin, a contaminant of trichlorophenol (TCP) while using TCP or a TCP derivative. PCP and several production contaminants have been implicated as animal carcinogens. A priori hypotheses were that the cohort would have elevated standardized mortality ratios (SMRs) for aplastic anemia, soft-tissue sarcoma, and non-Hodgkin lymphoma, as suggested by human studies, and for leukemia and liver, adrenal, thyroid, and parathyroid cancer, as suggested by animal studies. From 1940 to 2005 1165 deaths occurred with an overall SMR of 1.01 [95% confidence limits (CI), 0.95-1.07]. Overall cancer mortality (326 deaths, SMR 1.17, CI 1.05-1.31) was in statistically significant excess. There were excess deaths for trachea, bronchus and lung cancers (126 deaths, SMR 1.36, CI 1.13-1.62), non-Hodgkin lymphoma (17 deaths, SMR 1.77, CI 1.03-2.84), chronic obstructive pulmonary disease (63 deaths, SMR 1.38, CI 1.06-1.77), and medical complications (5 deaths, SMR 3.52, CI 1.14-8.22).The excess of cancers of a priori interest, non-Hodgkin lymphoma and leukemia, provide some support for the carcinogenicity of PCP, however, further studies with more detailed exposure assessment are needed.
    [Ruder AM, Yiin JH. 2011.Chemosphere. 83(6):851-61.]
  • Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study
    Study investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Overall cancer risk was slightly increased among terbufos users. Suggestive associations were observed between terbufos use and cancers of the prostate and lung, leukemia, and non-Hodgkin's lymphoma, although the exposure-response gradients were non-monotonic and p for trends were not significant. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.
    [Bonner, M.R., et al. 2010. Cancer Causes Control 21(6):871-7]
  • High risk occupations for non-Hodgkin's lymphoma in New Zealand: case-control study.
    Although pesticides are not specifically implicated, a New Zealand case control occupational study does find an elevated NHL risk for field crop and vegetable growers (OR 2.74) and horticulture and fruit growing (OR 2.28), particularly for women (OR 3.44).
    [Mannetje, A., et al. 2008. Occupational and Environmental Medicine 65:354-363]
  • Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.
    A Swedish population based case-control study of male and female NHL patients finds the highest risk is for exposure to: herbicides; MCPA with a latency period greater than ten years; glyphosate ; and, glyphosate exposure with a latency period of greater than ten years . When different NHL subtypes are analyzed: (a) diffuse large B-cell lymphoma is significantly associate with exposure to phenoxyacetic acids and especially for MCPA; (b) small lymphocytic lymphoma/chronic lymphocytic leukemia is associated with exposure to phenoxy herbicides, MCPA , and glyphosate ; (c) the category “other specific B-cell lymphoma (mantle cell lymphoma, marginal zone lymphoma)” an association is found for exposure to phenoxyacetic acids, MCPA and glphyosate; and (d) the category “unspecific NHL” subtypes are associated with herbicides, phenoxyacetic acids, MCPA and glyphosate.
    [Eriksson, M., et al. 2008. Int J Cancer 123(7):1657-1663]
  • Atopy, exposure to pesticides and risk of non-Hodgkin lymphoma
    Although the Australian population based case control study did not find a clear connection with asthma and pesticide exposure and NHL, it did find an increased risk of NHL with occupational pesticide exposure and a history of asthma as well as with occupational pesticide exposure an no history of asthma.
    [Vajdic, C.M., et al. 2007. Int J Cancer 120(10):2271-2274]
  • Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE)
    A case-control study in France finds prenatal insecticide use is significantly associated with childhood lymphoblastic and myelobastic NHL, mainly for Burkitt lymphoma, and finds paternal household use of pesticides is associated with NHL. Household use of any pesticide during pregnancy is significantly more frequent in NHL cases.
    [Rudant, J., et al. 2007. Environmental Health Perspectives 115(12):1787-1793]
  • Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study
    A NIH prospective cohort study of licensed pesticide applicators in Iowa and North Carolina finds a significant increase in risk for NHL and lindane.
    [Purdue, M.P., et al. 2007. Int J Cancer 120(3):642-649]
  • Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies
    A meta-analysis of 13 case-control studies on hematopoeietic cancers finds that occupational pesticide exposure greater than ten years significantly increases risk of NHL (OR 1.65).
    [Merhi, M, et al. 2007. Cancer Causes Control 18(10):1209-1226]
  • Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma.
    A population based, case control study in Nebraska looking at different molecular subtypes of NHL discovered that the risk of t(14;18)-positive NHL subtype is significantly elevated among farmers who used animal insecticides (OR 2.6), crop insecticides (OR 3.0), herbicides (OR 2.9) and fumigants (5.0 OR) and that there was no increased risk of t(14;18)-negative NHL subtype for these pesticides, which may explain some of the inconsistencies in epidemiological study of NHL and pesticide exposure. They also find that the risk increases with longer duration of use
    [Chiu, B., et al. 2006. Blood 108(4):1363-1369]
  • Cancer and pesticides: an overview and some results of the Italian multicenter case-control study on hematolymphopoietic malignancies
    A population based case-control study in Italy finds a significant increase in risk of NHL for occupational exposure to 2,4D.
    [Miligi, L., et al. 2006. Ann N Y Acad Sci 1076:366-377]
  • Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men
    A study using three National Cancer Institute case-controls of NHL in Iowa, Minnesota, Kansas, and Nebraska farmers finds coumaphos (OR 1.7), diazinon (OR 1.7), and glyphosate (OR 1.6) are associated with an increase in NHL incidence.
    [De Roos, A.J., et al. 2003. Occupational and Environmental Medicine 60(9):e11]
  • Exposure to pesticides as risk factor for non-Hodgkin's lymphoma and hairy cell leukemia: pooled analysis of two Swedish case-control studies.
    A pooled analysis on two Swedish case-control studies of NHL and hairy cell leukemia, a NHL subtype, finds that cancer registrants are more likely to have been exposued to herbicides; especially for glyphosate and MCPA; and, fungicides.
    [Hardell, L., et al. 2002. Leuk Lymphoma 43(5):1043-1049]
  • Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma.
    A study using a case control study of amle farmers in Iowa and Minnesota finds that the t(14;18)-positive subtypes of NHL is associated with farming (OR 1.4), lindane (OR 2.3), atrazine (OR 1.7) and fungicides (OR 1.8) and no association with t(14;18)-negative NHL
    [Schroeder, J., et al. 2001. Epidemiology 12(6):701-709]
  • Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.
    A Canadian multi-center population based incident case control study among men finds an increase risk of NHL for exposure to dicamba, carbamates, OPs, amide fungicides and fumigant carbon tetrachloride, mecoprop, malathion and carbaryl.
    [McDuffie, H., et al. 2001.Cancer Epidemiology, Biomarkers & Prevention 10:1155-1163]
  • Leukemia and Non-Hodgkin's Lymphoma in Childhood and Exposure to Pesticides: Results of a Register-based Case-Control Study in Germany
    A population-based case-control study in West Germany finds that insecticide use at home, whether applied by a professional pesticide applicator or a parent more than once a year or more than 10 times a year, is associated with childhood lymphoma.
    [Meinert, R., et al. 2000. American Journal of Epidemiology 151(7):639-646]
  • Pesticide exposures in children with non-Hodgkin lymphoma.
    A case-control study in the U.S. finds a significant association between risk of childhood NHL and frequency of reported prenatal home pesticide use, and professional treatments in the home. Postnatal home pesticide exposure also shows a significant association . In children, elevated risk for T-cell, B-cell lymphomas, lymphoblastic, large cell, and Burkitt morphologies are found.
    [Buckley, J.D., et al. 2000. Cancer 89(11):2315-2321]
  • A case-control study of non-Hodgkin lymphoma and exposure to pesticides
    A population based case-control study in Sweden finds an increased risk for NHL for people exposed to herbicides, specifically significant is exposure to MCPA, and fungicides.
    [Hardell, L., et al. 1999. Cancer 85(6):1353-1360]
  • Meta-analyses of non-Hodgkin's lymphoma and farming.
    A meta-analyses of 36 studies on NHL and farming suggests that male U.S. farmers have a slightly elevated risk of NHL.
    [Khuder, S.A., et al 1998. Scand J Work Environ Health 24(4):255-261]
  • Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
    A cohort study of cancer in offspring of parents working in Norway horticulture finds parental pesticide purchase associated with childhood NHL.
    [Kristensen, P., et al. 1996. Int J Cancer 65(1):39-50]
  • Cancer incidence among Icelandic pesticide users
    A small cohort study in Iceland shows that female licensed pesticide applicators for agricultural purposes have a significant increased incidence for cancers of the lymphatic and hematopoietic tissue in women.
    [Zhong, Y. and Rafnsson, V. 1996. International Journal of Epidemiology 25(6):1117-1124.]
  • Farming, pesticide use and hairy-cell leukemia.
    A significant association is found between HCL and exposure to pesticides used in farming (OR ranges between 1.5 to 2.4, depending on the type of pesticide). Orgaonphosphates were positively associated with HCL.
    [Clavel, J., et al. 1996. Scand J Work Environ Health 22(4):285-293]
  • Proportionate mortality study of golf course superintendents.
    A proportionate mortality study of a cohort of 686 golf course superintendents finds an elevated number deaths from brain cancer (PMR 234), large intestine cancer (PMR 175), NHL (PMR 237), and prostate cancer (PMR 293).
    [Kross, B.C., et al. 1996. Am J Ind Med 29(5):501-506]
  • Non-Hodgkin's lymphoma and agricultural practices in the prairie provinces of Canada.
    A follow-up to a previous cohort study in Canada finds a significant increase risk for fatal NHL for male farmers according to acres sprayed herbicides
    [Morrison, H.I., et al. 1994. Scand J Work Environ Health 10(1):42-47]
  • The role of agricultural pesticide use in the development of non-Hodgkin's lymphoma in women
    A population-based case control study in Nebraska finds that NHL risk is significantly increased for woman who handle OP insecticides, for use of chlorinated hydrocarbon insecticides, and for chlorinated hydrocarbon insecticide use on cattle. The study finds that pesticide related risk are grater for woman with a family history of cancer.
    [Zahm, S., et al. 1993. Archives of Environmental Health 48(5):353-358]
  • Herbicides and Cancer
    A literature review of epidemiological studies finds “reasonable evidence suggesting that occupational exposure to phenoxy herbicides results in increased risks of developing [NHL]
    [Morrison, H.I., et al. 1992. J Natl Cancer Inst 84(24):1866-1874]
  • Pesticides and Other Agricultural Risk Factors for Non-Hodgkin's Lymphoma among Men in Iowa and Minnesota
    A population based study of white male farmers finds a significant increase in risk for (a) diffuse NHL and organophosphates (OP) on crops, non-halogenated aliphatic OP on crops, cyclodiene chlorinated hydrocarbons used on livestock, and triazine herbicides; (b) small lymphocytic NHL with “natural product insecticides used on livestock” (although nowhere in the study does it define “natural”), and halongenated aromatic OP for livestock); and, (c) other and unclassified forms of NHL and chlorinated hydrobarbon insecticides for crops, cyclodienes for crops, and halogenated aliphatic OPs used on livestock
    [Cantor, K., et al. 1992. Cancer Research 52:2447-2455]
  • A case-control study of non-Hodgkin's lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska.
    A population based case-control study in Nebraska finds a slight increase NHL risk for men who mix or apply 2,4-D. A significant risk is found for: men who mix or apply 2,4-D for 20 days or more a year; men who mix or apply 2,4-D and fungicides; men who mix or apply 2,4-D and OPs; and, men who mix or apply 2,4-D, fungicides and OPs.
    [Zahm, S., et al. 1990. Epidemiology 1(5):349-356]
  • Cancer mortality in the U.S. flour industry
    A nested case control mortality study of workers employed in U.S. flour mills, where according to the study author’s, “pesticides are used more frequently than in other segments of the industry,” an increased risk for NHL (OR 4.2) is found.
    [Alavanja, M.C., et al. 1990. J Natl Cancer Inst 82(10):840-848]
  • Mortality study of Canadian male farm operators: cancer mortality and agricultural practices in Saskatchewan.
    A cohort mortality study of male Saskatchewan farmer finds a significant dose-response relationship is found between risk of NHL and acres sprayed with herbicides
    [Wigle, D., et al. 1990. Journal of the National Cancer Institute 82(7):575-582]
  • Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington.
    A population-based case-control study in Washington state finds an elevated risk of NHL among male forestry herbicide applicators and for men that are potential exposed to phenoxy herbicides in any occupation for 15 or more years prior to their cancer diagnosis.
    [Woods, J.S., et al. 1987. J Natl Cancer Inst 78(5):899-910]
  • Agricultural herbicide use and a risk of lymphoma and soft-tissue sarcoma.
    A population based case control study in Kansas finds farm herbicide use increases risk associated with NHL; risk increased significantly for those men exposed to herbicides more than 20 days a year; and, those men that frequently mixed or applied herbicides themselves also have a significant increased risk to phenoxyacetic acid herbicides, specifically 2,4D.
    [Hoar, S., et al. 1986. Journal of the American Medical Association 259(9): 1141-1147]
  • Malignant lymphoma and multiple myeloma linked with agricultural occupations in a New Zealand Cancer Registry-based study.
    A case-control study of New Zealand agriculture and forestry workers finds a significant excess of patients with nodular lymphoma, mycosis fungoldes, and NHL.
    [Pearce, N.E., et al. 1985. Am J Epidemiol 121(2):225-237]
  • Farming and mortality from non-Hodgkin's lymphoma: A case-control study
    A case control mortality study in Wisconsin finds an elevated risk among farmers for reticulum-cell sarcoma, a subtype of NHL, in counties with grain acres treated with insecticides .
    [Cantor, KP. 1982. Int J Cancer 29(3):239-247]

Melanoma

  • Residential and occupational exposure to pesticides may increase risk for cutaneous melanoma: a case-control study conducted in the south of Brazil.
    Incidences of primary cutaneous melanoma (CM) have risen over the last few decades, mainly among populations of White European extraction. Some risk factors for melanoma have been clearly established, but other potential risk factors, such as exposure to pesticides, are currently under study.A case-control study on melanoma was conducted during 2012 and 2013 at three dermatological reference centers in Porto Alegre, Brazil. A total of 191 CM patients and sex- and age-matched control subjects were enrolled in the study. Subjects exposed to pesticides had twice the level of risk for melanoma (odds ratio [OR] 2.03). When pesticides were used indoors for >10 years, the risk for CM increased further (OR 2.84). A high frequency of indoor use of pesticides (four or more times per year) was associated with a 44% increase in the risk for melanoma (OR 1.44). The domestic use of pesticides outdoors was not associated with increased risk. Subjects exposed to pesticides at an occupational level were at four times greater risk than subjects who were not occupationally exposed (OR 4.23).These findings indicate that the general use of pesticides, particularly indoor domestic use, frequently and over a long period, may be an independent environmental risk factor for CM.
    [Segatto MM, Bonamigo RR, Hohmann CB, Müller KR, et al. 2015. Int J Dermatol. doi: 10.1111/ijd.12826]
  • Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.
    Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. Objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate). These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. Study found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. Data support the hypothesis that pesticides can trigger some molecular events involve malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.
    [Chorfa A, Bétemps D, Morignat E, Lazizzera C, et al. 2013. Toxicol Sci. 133(2):289-97.]
  • Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: a preliminary study.
    This preliminary study examined the relationship between organochlorine compounds(OCC) residues in plasma and risk of cutaneous malignant melanoma (CMM) adjusting for sun sensitivity and sun exposure. A case-control study of 80 CMM patients and 310 control subjects was conducted. Lifetime sun exposure information, along with data on pigmentation variables and sun sensitivity data was collected, along with a blood sample. Strong associations were seen between risk of CMM and plasma levels of non-dioxin-like PCBs (Adjusted OR = 7.02) and several PCB congeners, organochlorine pesticides or metabolites. These associations persisted after control for sun sensitivity and sun exposure. Results from this investigation require independent confirmation in larger studies. However, they suggest that environmental factors other than UV radiation may play a role in genesis of CMM, and indicate that it may be productive to search for further agents which might increase risk.
    [Gallagher RP, Macarthur AC, Lee TK, Weber JP, et al. 2011. Int J Cancer. 128(8):1872-80]
  • Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the Agricultural Heath Study
    Research finds found significant associations between cutaneous melanoma and maneb/mancozeb (>or= 63 exposure days: OR = 2.4), parathion (>or= 56 exposure days: OR = 2.4), and carbaryl (>or= 56 exposure days: OR = 1.7). Other associations with benomyl and ever use of arsenical pesticides are also suggested.
    [Dennis LK, et al. 2010. Environ Health Perspect. 118(6):812-7. Epub 2010 Feb 17.]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • Carbaryl exposure and incident cancer in the Agricultural Health Study
    Using the Agricultural Health Study cohort of pesticide applicators and looking at carbaryl exposure, finds that carbaryl exposure is associated with an elevated risk to melanoma, even after adjusting for sunlight exposure.
    [Mahajan, R., et al. 2007. Int J Cancer 121(8):1799-1805.]
  • The association between residential pesticide use and cutaneous melanoma
    A case-control study of cutaneous melanoma finds an increased risk for indoor pesticide use four times a year (OR 2.18) compared to one time a year and for those exposed for 10 years or more an almost two and half times the risk as those exposed for less than 10 years indicating residential pesticide exposure may be a factor for cutaneous melanoma.
    [Fortes, C., et al. 2007. Eur J Cancer 43(6):1066-1075.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for skin melanoma cancer in males (OR 1.77).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]

Mouth Cancer

Multiple Myeloma

  • Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study (AHS) data.
    A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993-2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use.
    [Sorahan T .2015. Int J Environ Res Public Health. 12(2):1548-59.]
  • Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses
    This systematic review aims to synthesize meta-analyses examining risk factors for MM so as to provide a comprehensive, parsimonious summary of the current evidence. Eligible meta-analyses were sought in PubMed adopting a predefined. Among the 22 ultimately included meta-analyses, 9 examined occupational factors, 4 assessed aspects of lifestyle (smoking, alcohol, body mass index), 5 evaluated the presence of other diseases, and 4 addressed genetic factors as potential risk factors of MM. A vast compendium of significant associations arose, including farming, exposures to chemicals or pesticides, overweight and obesity, pernicious anemia, gene promoter methylation, and polymorphisms. In conclusion, MM is a multifactorial disease, encompassing a wide variety of risk factors that span numerous life aspects. Further accumulation of evidence through meta-analyses is anticipated in this rapidly growing field.
    [Sergentanis TN, Zagouri F, Tsilimidos G, et al. 2015. Clin Lymphoma Myeloma Leuk. 15(10):563-577.e3]
  • Multiple myeloma and occupation: a pooled analysis by the International Multiple Myeloma Consortium.
    Authors investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case-control studies. Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50), while other farming jobs did not. Metal processors, female cleaners, and high level exposure to organic solvents also showed moderately increased risks. Additional case-control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.
    [Perrotta C, Kleefeld S, Staines A, Tewari P, De Roos AJ, et al 2013. Cancer Epidemiol.37(3):300-5.]
  • Multiple pesticide exposures and the risk of multiple myeloma in Canadian men
    Multiple myeloma (MM) has been linked to certain agricultural exposures, including pesticides. This analysis aimed to investigate the association between lifetime use of multiple pesticides and MM risk using two exposure metrics: number of pesticides used and days per year of pesticide use. A frequency-matched, population-based case-control study was conducted among men in six Canadian provinces between 1991 and 1994. Positive trends in risk were observed for fungicides (ptrend=0.04) and pesticides classified as probably carcinogenic or higher (ptrend=0.03). Excess risks of MM were observed among men who reported using at least one carbamate pesticide (OR=1.94), one phenoxy herbicide (OR=1.56) and ≥3 organochlorines (OR=2.21, 1.05-4.66). Significantly higher odds of MM were seen for exposure to carbaryl (OR=2.71) and captan (OR=2.96). Use of mecoprop for >2 days per year was also significantly associated with MM (OR=2.15). Focusing on multiple pesticide exposures is important because this more accurately reflects how exposures occur in occupational settings. Significant associations observed for certain chemical classes and individual pesticides suggest that these may be MM risk factors.
    [Kachuri L, Demers PA, Blair A, Spinelli JJ, et al. 2013. Int J Cancer. 133(8):1846-58.]
  • Multiple myeloma and exposure to pesticides: a Canadian case-control study.
    The objective of this study was to investigate the putative associations of specific pesticides with multiple myeloma. A matched, population-based, case-control study was conducted among men residing in six Canadian provinces (Quebec, Ontario, Manitoba, Saskatchewan, Alberta, and British Columbia). Exposure to pesticides grouped into major chemical classes resulted in increased risk being detected only for carbamate insecticides. An exposure to fungicide captan was positively associated with the incidence of multiple myeloma. While an exposure to carbaryl was associated with the incidence of multiple myelome with borderline significance. The authors further suggest that certain pesticide exposures may have a role in multiple myeloma etiology, and identify specific factors warranting investigation in other populations.
    [Pahwa P, Karunanayake CP, Dosman JA, et al. 2012. J Agromedicine. 17(1):40-50.]
  • Multiple Myeloma and lifetime occupation: results from the EPILYMPH study.
    The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case-control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set.A low level of education was associated with MM. An increased risk was observed for general farmers and cleaning workers adjusting for level of education. Risk was also elevated, although not significant, for printers. Pesticide exposure over a period of ten years or more increased MM risk. These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.
    [Perrotta C, Staines A, Codd M, Kleefeld S, Crowley D, et al. 2012. J Occup Med Toxicol. 7(1):25.]
  • Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study
    Exposure to certain pesticides doubles one’s risk of developing an abnormal blood condition called MGUS (monoclonal gammopathy of undetermined significance) compared with individuals in the general population.
    [Landgren, O, et al. 2009. Blood, Vol. 113, No. 25, pp. 6386-6391]
  • Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden
    A historical cohort study of occupation exposure in Sweden finds an excess risk among agricultural, horticultural and forestry workers in men and “occasional, although intense, exposure to pesticides is also associated with riks of myeloma.”
    [Lope, V., et al. 2008. Cancer Epidemiol Biomarkers Prev 17(11):3123-3127.]
  • Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies
    A meta-analysis of 13 case-control studies on hematopoeietic cancers (leukemia, NHL, and multiple myeloma) published between 1990 and 2005 finds a significant positive association for occupational pesticide exposure of more than 10 years and all hematopoietic cancers (OR 2.18).
    [Merhi, M, et al. 2007. Cancer Causes Control 18(10):1209-1226]
  • Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States)
    Cancer mortality among Iowa farmers shows an excess of deaths for multiple myeloma (1.17 PMR).
    [Cerhan, J.R., et al. 1998. Cancer Causes Control 9(3):311-319.]
  • Incidence and risk factors of cancer among men and women in Norwegian agriculture
    Agricultural exposure to pesticides for those cultivating potatoes is linked to multiple myeloma in males and females.
    [Kristensen, P., et al. 1996. Dcand J Work Environ Health 22(1):14-26.]
  • Malignant lymphoma and multiple myeloma linked with agricultural occupations in a New Zealand Cancer Registry-based study.
    A case-control study of New Zealand agriculture and forestry workers finds a significant excess of patients with multiple myeloma (OR 2.22).
    [Pearce, N.E., et al. 1985. Am J Epidemiol 121(2):225-237]
  • Selected cancer mortality and farm practices in Iowa
    A mortality study of Iowan farmers who died between 1964 and 1978 finds an elevated mortality from multiple myeloma in association with herbicide and insecticide use.
    [Burmeister, L.F., et al. 1983.Am J Epidemiol 118(1):72-77.]

Neuroblastoma

Oesophageal Cancer

  • Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.
    In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working.
    [Meyer A, Alexandre PC, Chrisman Jde R, et al. 2011. Int J Hyg Environ Health. 214(2):151-5.]
  • Pesticide sales and adult male cancer mortality in Brazil.
    A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.
    [Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]
  • Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma
    A Swedish population based case control study assessing cumulative airborne occupational exposure finds a positive association between high exposure to pesticides and risk of oesophageal (OR 2.3) and cardia adenocarcinoma (OR 2.1).
    [Jansson, C., et al. 2006. Occup Environ Med 63(2):107-112.]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for oesophagus cancer in males (OR 1.69).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]

Ovarian Cancer

  • Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study
    Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. This study evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).Authors observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.
    [Lerro CC, Koutros S, Andreotti G, Friesen MC, et al. 2015. Occup Environ Med. 72(10):736-44]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for oesophagus cancer in males (OR 1.69).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]
  • Triazine herbicides and ovarian epithelial neoplasms
    A population-based case referent study finds a significant increased risk for ovarian neoplasm (relative risk 2.7).
    [Donna, A., et al. 1990. Scand J Work Environ Health 15(1):47-53.]

Pancreatic Cancer

  • Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer.
    Study examined pancreatic cancer (PC) risk with self-reported exposures to chemicals and heavy metals.
    The design was a clinic-based, case-control study of data collected from 2000 to 2014 at Mayo Clinic in Rochester, Minnesota, USA. Self-reported regular exposure to pesticides was associated with increased odds of PC (OR 1.21). Regular exposure to asbestos (OR 1.54), benzene (OR 1.70, and chlorinated hydrocarbons (OR 1.63) also was associated with higher odds of PC. These findings add to the limited data suggesting that exposure to pesticides, asbestos, benzene, and chlorinated hydrocarbons may increase PC risk. They further support the importance of implementing strategies that reduce exposure to these substances.
    [Antwi SO, Eckert EC, Sabaque CV, Leof ER, et al. 2015. Cancer Causes Control. 26(11):1583-91.]
  • Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort.
    Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, authors conducted a case-control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. Among pesticide applicators, 2 herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity-weighted lifetime use showed a statistically significant exposure-response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0-fold risk compared with never users, and those in the top half of lifetime EPTC use had a 2.56-fold risk compared with never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer.
    [Andreotti G, Freeman LE, Hou L, Coble J, Rusiecki J, et al. 2009. Int J Cancer. 124(10):2495-500.]
  • Pesticide sales and adult male cancer mortality in Brazil.
    A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.
    [Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]
  • Lifestyle, occupational, and reproductive factors in relation to pancreatic cancer risk
    A study identifying risk factors for pancreatic cancer in Egypt finds an elevated risk for those individuals exposed to pesticides (OR 2.6).
    [Lo, A.C., et al. 2007. Pancreas 35(2):120-129.]
  • Occupational exposure to pesticides and pancreatic cancer
    Excess risk is found for occupational exposure to fungicides (OR 1.5) and herbicides (OR 1.6).
    [Ji, B.T., et al. 2001. Am J Ind Med 39(1):92-99.]
  • Risk of pancreatic cancer and occupational exposures in Spain
    In a small study, occupational exposures to pesticides cause a three-fold increased risk for pancreatic cancer. For each type of pesticide group, moderately increased odds ratios were apparent in the high-intensity category, highest for arsenical pesticides (OR 3.4), and ‘other pesticides’ (OR 3.17).
    [Alguacil, J., et al. 2000. Ann Occup Hyg 44(5):391-403.]
  • Mortality among aerial pesticide applicators and flight instructors: follow-up from 1965-1988
    A retrospective cohort mortality study of aerial pesticide applicator pilots finds a significantly elevated risk for pancreatic cancer (risk ratio 2.71).
    [Cantor, K.P. and Silberman, W. 1999. Am J Ind Medicine 36(2):239-47]
  • Pancreatic cancer in industrial branches and occupations in Finland
    Finnish study finds a more than six-fold increased risk for male gardeners to pancreatic cancer.
    [Partanen, T., et al 1994. Am J Ind Med 25(6):851-866.]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a significantly increased risk of pancreatic cancer, as well as other cancers, among licensed pesticides users with greater than 10 years’ experience.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]
  • Cancer mortality in the U.S. flour industry
    A study of U.S. flour mill workers finds an two-fold increased risk for pancreatic cancer (OR 2.2.) believed to be related to pesticide exposure.
    [Alavanja, M.C., et al. 1990. J Natl Cancer Inst 82(10):840-848]

Prostate Cancer

  • Chronic chlorpyrifos exposure does not promote prostate cancer in prostate specific PTEN mutant mice.
    Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Authors used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers.
    [Svensson RU, Bannick NL, Marin MJ, et al. 2013. J Environ Pathol Toxicol Oncol.32(1):29-39]
  • Farming, reported pesticide use, and prostate cancer.
    Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. This study performed a meta-analysis to summarize the association of farming and prostate cancer. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia. Reported pesticide exposure was inversely associated with prostate cancer, whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides.
    [Ragin C, Davis-Reyes B, Tadesse H, et al. 2013. Am J Mens Health.7(2):102-9]
  • Genetic susceptibility loci, pesticide exposure and prostate cancer risk.
    Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. Authots evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. Among men carrying two T alleles in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use. Among men carrying two A alleles in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.
    [Koutros S, Berndt SI, Hughes Barry K et al. 2013. PLoS One. 8(4):e58195]
  • Pesticide exposure and inherited variants in vitamin d pathway genes in relation to prostate cancer.
    Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties.Study hypothesizes that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants. Study evaluated interactions between 41 pesticides and 152 single-nucleotide polymorphisms (SNP) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of Caucasian pesticide applicators within the Agricultural Health Study.Five significant interactions displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB, and GC). In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, an SNP previously linked to lower circulating vitamin D levels, modified pesticide associations with prostate cancer risk. Because this study is the first to examine this relationship, additional studies are needed to rule out chance findings.
    [Karami S, Andreotti G, Koutros S, Barry KH, et al. 2013.Cancer Epidemiol Biomarkers Prev. 22(9):1557-66]
  • Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.
    Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos, malathion and terbufos. The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer. This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer.
    [Koutros S, Beane Freeman LE, Lubin JH, et al. 2013. Am J Epidemiol. 177(1):59-74]
  • Environmental exposures and prostate cancer.
    Many malignancies have been linked to specific environmental exposures. Several environmental and occupational factors have been studied for an association to prostate cancer (CaP) risk. These include Agent Orange exposure, farming and pesticides, sunlight/ultraviolet radiation, as well as trace minerals used in tire and battery manufacturing. This manuscript reviews the literature on these environmental exposures and CaP.
    [Mullins JK, Loeb S. 2012. Urol Oncol. 30(2):216-9]
  • Prostate cancer and toxicity from critical use exemptions of methyl bromide: environmental protection helps protect against human health risks.
    Authors performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. Study focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Out of the 542 peer reviewed publications between 1990-2011, 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.
    [Budnik LT, Kloth S, Velasco-Garrido M, Baur X. 2012. Environ Health.11:5]
  • Genetic variation in base excision repair pathway genes, pesticide exposure, and prostate cancer risk.
    Authors evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for low and high use compared with no use, whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. These findings regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.
    [Barry KH, Koutros S, Berndt SI, Andreotti G, et al. 2011. Environ Health Perspect. 119(12):1726-32]
  • Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California.
    In a population-based case-control study in California's intensely agricultural Central Valley (2005-2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide and a group of organochlorines) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride).
    This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.
    [Cockburn M, Mills P, Zhang X, et al. 2011. Am J Epidemiol. 173(11):1280-8]
  • Prostate cancer risk and exposure to pesticides in British Columbia farmers.
    Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. The aim of this study was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides. A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants' lifetime cumulative exposure to approximately 180 active compounds in pesticides. The significant association between prostate cancer risk and exposure to DDT, simazine, and lindane is in keeping with those previously reported in the literature. Authors also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in this study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.
    [Band PR, Abanto Z, Bert J, et al.2011. Prostate. 71(2):168-83]
  • Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer.
    Researchers evaluated pesticide-SNP interactions between 45 pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and 1444 controls in the Agricultural Health Study. A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase; men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk. Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased prostate cancer risk was observed with high, compared with no, petroleum oil/petroleum distillate, or terbufos use. Researchers observed several pesticide-SNP interactions in oxidative stress and phase I/II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.
    [Koutros S, Andreotti G, Berndt SI, et al. 2011. Pharmacogenet Genomics. 21(10):615-23]
  • An update of cancer incidence in the Agricultural Health Study.
    The objective was to reevaluate cancer incidence among Agricultural Health Study participants. A significant excess of prostate cancer was seen for private and commercial applicators. Excesses were observed for lip cancer and multiple myeloma among private applicators from North Carolina and for marginal zone lymphoma among Iowa spouses. Although lower rates of smoking and increased physical activity probably contribute to the lower overall cancer incidence, agricultural exposures including pesticides, viruses, bacteria, sunlight, and other chemicals may increase risks for specific cancer sites.
    [Koutros S, Alavanja MC, Lubin JH, et al. 2010. J Occup Environ Med. 52(11):1098-105]
  • Chlordecone exposure and risk of prostate cancer.
    Study analyzed the relationship between exposure to chlordecone and the risk of prostate cancer. Researchers investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status. Study found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration and for cumulative exposure index. Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer.
    [Multigner L, Ndong JR, Giusti A, et al. 2010. J Clin Oncol. 28(21):3457-62]
  • Coumaphos exposure and incident cancer among male participants in the Agricultural Health Study (AHS).
    Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer. This study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993-1999) and later (2000-2005) in AHS follow-up. This study included 47,822 male licensed pesticide applicators.
    Approximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early periods of follow-up. Across all years, this association was statistically significant. Coumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility.
    [Christensen CH, Platz EA, Andreotti G, et al. 2010. Environ Health Perspect. 118(1):92-6]
  • Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study.
    Study investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Overall cancer risk was slightly increased among terbufos users. Suggestive associations were observed between terbufos use and cancers of the prostate and lung and leukemia and non-Hodgkin's lymphoma, although the exposure-response gradients were non-monotonic and p for trends were not significant. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.
    [Bonner MR, Williams BA, Rusiecki JA, et al. 2010. Cancer Causes Control. 21(6):871-7]
  • Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer.
    In the Agricultural Health Study, a prospective study of licensed pesticide applicators,authors observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, study evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. Authors observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.
    [Koutros S, Beane Freeman LE, Berndt SI, et al. 2010. Cancer Res. 70(22):9224-33]
  • Does exposure to agricultural chemicals increase the risk of prostate cancer among farmers?
    Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980's, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. There was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides, as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions. The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need further confirmation in larger samples.
    [Parent ME, Désy M, Siemiatycki J. 2009. Mcgill J Med. 12(1):70-7]
  • Pesticide sales and adult male cancer mortality in Brazil.
    A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.
    [Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]
  • Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer
    Twice as many Vietnam veterans exposed to Agent Oragne were identified with prostate cancer (239 vs 124 unexposed men, respectively; (OR 2.19). Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts.
    [Chamie, K., deVere White, R. W., Lee, D., Ok, J. and Ellison, L. M. 2008. Cancer, 113: 2464–2470.]
  • A case-control study of farming and prostate cancer in African-American and Caucasian men
    A population-based case-control study in South Carolina finds farming is associated with increase risk of prostate cancer in Caucasians (OR 1.8) but not African-Americans. The study also finds that farmers who mixed or applied pesticides have a greater risk (OR 1.6); and, the increased risk is found only for those farming less than 5 years. The authors conclude that the racial differenc
    [Meyer, T.E., et al. 2007. Occup Environ Med 64(3):155-160.]
  • Prostate cancer and exposure to pesticides in agricultural settings
    Individuals that have worked in agriculture is associated with a 40% increased risk of prostate cancer (OR 1.4)
    [Settimi, L., et al. 2003. Int J Cancer 104(4):458-461.]
  • Prostate cancer risk in California farm workers
    Hispanic farmworkers are found to be at an increased risk for prostate cancer when exposed to relatively high levels of certain organochlorines, organophosphates, fumigants and triazine herbicides.
    [Mills, P.K. and Yang, R. 2003. J Occup Environ Med 45(3):249-258.]
  • Use of agricultural pesticides and prostate cancer risk in the Agricultural Health Study cohort
    A prospective cohort study of Iowa and North Carolina male pesticide applicators finds that the two highest exposure scenarios (OR 2.73 and 3.47) significantly increase risk for prostate cancer. Significant interaction odds ratios occurred among persons who used butylate (OR 1.93); four organophosphorothioate insecticides including coumaphos (OR 2.58), fonofos (OR 2.04), chlorpyrifos (OR 1.65), and phorate (OR 1.64); and a pyrethroid, permethrin (for animal use) (OR 2.31).
    [Alavanja, M., et al. 2003. American Journal of Epidemiology 157:800-814.]
  • Cancer incidence among triazine herbicide manufacturing workers
    Workers at a triazine manufacturing plant are found to have an elevated number of prostate cancer cases.
    [MacLennan, P.A., et al. 2002. J Occup Environ Med 44(11):1048-1058.]
  • Occupation and prostate cancer
    Occupational exposures to pesticides including farmers, forestry workers or horticulturists finds a slight increased risk among farmers, speculating that certain pesticides act as hormone modifiers and influence the prostate cancer risk.
    [Parent, M. and Siemiatycki, J. 2001. Epidemiologic Reviews 23(1):138-143.]
  • Occupation and prostate cancer risk in Sweden
    Swedish stuy shows significantly elevated standardized incidence ratio are found in farmers and ceratin occupations and industries with exposures to herbicides and fertilizers. Results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks.
    [Sharma-Wagner, S., et al. 2000. J Occup Environ Med 42(5):517-525.]
  • Cancer incidence in a cohort of licensed pesticide applicators in Florida
    A standardized incidence ratio anaylsis (SIR) of licensed pesticide applicators in Florida, compared with Florida’s general population, finds an increased incidence rate for prostate cancer (SIR 1.91).
    [Fleming, L., et al. 1999. Journal of Occupational and Environmental Medicine 41(4):279-288.]
  • Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States)
    A cancer mortality study of Iowa farmers shows an excess of deaths for cancers of the prostate (1.26 PMR).
    [Cerhan, J.R., et al. 1998. Cancer Causes Control 9(3):311-319.]
  • Correlation analysis of pesticide use data and cancer incidence rates in California counties.
    An ecological study in California analyzing data on pesticide use and cancer incidence finds a correlation between black males diagnosed with prostate cancer and atrazine and captan.
    [Mills, P.K. 1998. Arch Environ Health 53(6):410-413]
  • Prostate cancer in pesticide applicators in Swedish agriculture
    A cohort of over 20,000 licensed agriculture pesticide applicators in Sweden finds a statistically significant increased risk of prostate cancer.
    [Dich, J., and Wiklund, K. 1998. Prostate 34(2):100-112.]
  • Meta-analyses of prostate cancer and farming
    A meta-analyses of prostate cancer and farming studies between 1983 and 1994 finds a positive association between prostate cancer and farming, which the study authors attribute to exposure to hormonally active agricultural chemicals.
    [Keller-Byrne, J.E., et al. 1997. Am J Ind Med 31(5):580-586.]
  • Proportionate mortality study of golf course superintendents.
    A mortality study of a cohort of 686 deceased U.S. male golf course superintendents from the finds elevated levels for prostate cancer (PMR 293).
    [Kross, B.C., et al. 1996. Am J Ind Med 29(5):501-506]
  • Farming and prostate cancer among African-Americans in the Southeastern Untied States
    A study looking at African-American farmers shows further support that prostate cancer risk is associated with farming occupations.
    [Dosemeci, M., et al. 1994. Journal of the National Cancer Institute 86(22):1718-1719.]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a possible relationship between wheat crops and prostate cancer.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]
  • Farming and prostate cancer mortality
    A restrospective cohort study of male farmers find an increased risk associationed with acres of farmland sprayed with herbicides and dying from prostate cancer. No other farm activity examined in the study was associated with any detectable pattern of increased or decreased risk.
    [Morrison, H., et al. 1993. American Journal of Epidemiology 137(3):270-280.]
  • Mortality among white and nonwhite farmers in North Carolina, 1976-1978.
    A mortality study of farmers in North Carolina finds an increased frequency of prostate cancer among white decedents under 65 years of age (PMR 1.6).
    [Delzell, E., and Grufferman, S. 1985. Am J Epidemiol 121(3):391-402]

Sinonasal cancer

Soft Tissue Sarcoma

Stomach Cancer

  • Methyl bromide exposure and cancer risk in the Agricultural Health Study.
    Study used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use for low and high use compared with no use. No other sites displayed a significant monotonic pattern. Results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, study observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.
    [Barry KH, Koutros S, Lubin JH, et al. 2012. Cancer Causes Control. 23(6):807-18]
  • Agricultural exposures and gastric cancer risk in Hispanic farm workers in California
    Occupation in the citrus industry (OR 2.88) and in areas with high 2,4-D use (OR 1.85), and use of acaricide propargite (OR 2.86) or triflurin (OR 1.69) are associated gastric cancer.
    [Mills, P.K., and Yang, R.C. 2007. Environ Res 104(2):282-289.]
  • Associations between stomach cancer incidence and drinking water contamination with atrazine and nitrate in Ontario (Canada) agroecosystems, 1987-1991
    Drinking water contaminated with atrazine below the maximum allowable limits (50ng/l to 649ng/l) is associated with stomach cancer incidence.
    [Van Leeuwen, J.A., et al. 1999. International Journal of Epidemiology 28:836-840.]
  • Cancer among farmers in central Italy
    A case-referent study of Italian farmers finds a significantly increased risk of stomach cancer among farmers with greater than 10 years experience and among licensed pesticides users with greater than 10 years’ experience.
    [Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]

Testicular Cancer

  • Occupational and environmental exposures associated with testicular germ cell tumours: systematic review of prenatal and life-long exposures.
    Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of this review was to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale. Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene-environment interactions will be necessary to establish clear conclusion.
    [Béranger R, Le Cornet C, Schüz J, Fervers B. 2013. PLoS One. 8(10):e77130]
  • Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls.
    The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use. Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.
    [Giannandrea F, Gandini L, Paoli D, et al. 2011. J Environ Sci Health B. 46(8):780-7]
  • Cancer incidence in a cohort of licensed pesticide applicators in Florida
    Although small numbers Cancer incidence among licensed pesticide applicators in Florida is elevated for cervical cancer (SIR 3.69) and testicular cancer (SIR 2.48).
    [Fleming, L., et al. 1999. Journal of Occupational and Environmental Medicine 41(4):279-288.]
  • Correlation analysis of pesticide use data and cancer incidence rates in California counties.
    An ecological study in California analyzing data on pesticide use and cancer incidence finds a correlation between Hispanic males diagnosed with testicular cancer and atrazine.
    [Mills, P.K. 1998. Arch Environ Health 53(6):410-413]
  • Testicular cancer associated with employment in agriculture and oil and natural gas extraction
    A hospital-based case-control study find an increased risk for testicular cancer in men who work in the agricultural industry.
    [Mills, P.K., et al. 1984. Lancet 1(8370):207-210.]

Thyroid Cancer

  • Occupation and thyroid cancer.
    Here authors review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. They summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations.
    [Aschebrook-Kilfoy B, Ward MH, Della Valle CT, Friesen MC. 2014. Occup Environ Med. 71(5):366-80]
  • Nitrate intake and the risk of thyroid cancer and thyroid disease
    Study finds an increased risk of thyroid cancer with higher average nitrate levels in public water supplies (nitrate is a contaminant of drinking water in agricultural areas) and with longer consumption of water exceeding 5 mg/L nitrate-N (for >or=5 years at >5 mg/L, relative risk = 2.6).
    [Ward MH, et al. 2010. Epidemiology. 21(3):389-95]
  • Risk factors of thyroid tumors: role of environmental and occupational exposures to chemical pollutants.
    The rising incidence of thyroid cancer observed during the last few decades in most western countries is explained in large part by increasing numbers of diagnoses due to changes in medical screening practices. However, beside radiation exposure, exposure to environmental chemicals may also play a role in thyroid cancer etiology and in the increased incidence. This paper presents the main chemicals suspected to induce thyroid tumorigenesis, and epidemiological results on the association between chemical exposure and thyroid tumors.This review found that environmentally abundant chemicals may disrupt thyroid function and/or play a role in tumorigenesis through a variety of mechanisms. Epidemiological results provide insufficient evidence of a causal link between exposure to environmental chemicals and thyroid tumors, but raise the hypothesis of an increased risk of thyroid neoplasm for workers in the leather, wood, and paper industries, and those exposed to certain solvents and pesticides.
    [Leux C, Guénel P. 2010. Rev Epidemiol Sante Publique.58(5):359-67]
  • Thyroid disruption: mechanism and clinical implications in human health.
    Exposure to specific environmental toxins, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines, has been shown to interfere with the production, transportation, and metabolism of thyroid hormones by a variety of mechanisms. A broad range of chemicals, with structural similarity to thyroid hormone, have been shown to bind to thyroid receptors with both agonist and antagonist effects on thyroid hormone signaling. The incidence of thyroid disease in the United States, particularly for thyroid cancer and thyroid autoimmune disease, is increasing substantially. The evidence for the significant effects of background levels of thyroid-disrupting chemicals, the known pathways for thyroid disruptors, and the evidence and implications for neurodevelopmental damage due to thyroid-disrupting chemicals is reviewed.
    [Patrick L. 2009. Altern Med Rev. 14(4):326-46]
  • Mechanism of trifluralin-induced thyroid tumors in rats.
    Trifluralin has been reported to cause a significant increase in thyroid follicular cell tumors in male Fischer 344 rats. This study was designed to determine the mechanism of thyroid hyperactivity after trifluralin exposure. A group of 15 male Fischer 344 rats were exposed to trifluralin-fortified (6500 ppm) diet for 2 weeks. In the trifluralin treated rats, the serum T3 and T4 levels decreased by 17% and 90%, respectively and TSH increased by 37% more than the control rats. The decrease in total serum T3 and T4 levels in the trifluralin treated rats was due to enhanced peripheral metabolism and an increase in bile flow that results in a compensatory increase in TSH synthesis and secretion. The increased levels of TSH with chronic exposure to trifluralin would exert a continuous stimulation of the thyroid gland leading to cellular hypertrophy and proliferation predisposing to the development of follicular cell tumors in rats.
    [Saghir SA, Charles GD, Bartels MJ, et al. 2008. Toxicol Lett.180(1):38-45]
  • Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
    An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with moderate to high agricultural activity finds statistically significantly elevated risk for thyroid carcinomas (OR 3.0) at high agricultural activity (greater than 60 percent of the total county acreage is devoted to farming). An increased risk is also found for thyroid carcinomas and oat crop acreage (OR 2.0).
    [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
  • A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.
    Prolonged treatment with high doses of pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Treatment with pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T4) and/or triiodothyronine (T3). The effects of pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.
    [Finch JM, Osimitz TG, Gabriel KL, et al. 2006. Toxicol Appl Pharmacol.214(3):253-62]

Uterine Cancer

  • An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells.
    Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 microM) had a stimulatory effect on the growth of both cell lines at 24 h compared with controls by MTS (p < 0.01) and BrdU (p < 0.01) assays in hormonally responsive uterine leiomyoma (UtLM) cells and normal uterine smooth muscle cells (UtSMC). Data shows that Fen can stimulate the growth of both UtLM cells and UtSMC, which involves a combination of enhanced cell cycle progression and inhibition of apoptosis. Also this compound can increase collagen I expression, at both mRNA and protein levels. Results also indicate that Fen exposure could be considered a novel risk factor for uterine fibroids through molecular mechanisms that do not directly involve the ERs.
    [Gao X, Yu L, Castro L, Moore AB, et al. 2010. Toxicol Lett. 196(3):133-41]
  • Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
    A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for cancer of the corpus uteri (OR 1.78).
    [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]