14
Jan
Pesticides Harming Immune Cell Function Linked to Elevated Breast Cancer Rate in Young Women
(Beyond Pesticides, January 14, 2025) Women with occupational pesticide exposure have elevated rates of breast cancer, according to a study in Immunopharmacology and Immunotoxicology. Based on an analysis of clinicopathological data from 188 affected women, the study authors demonstrate “that occupational exposure to pesticides modifies the clinical presentation of disease in breast cancer patients, depending on their age at disease onset, affecting cytokine production, especially in those exhibiting early age at diagnosis.â€Â Â
“Breast cancer (BC) is the most common malignant neoplasm affecting women worldwide and the second leading cause of cancer-related death in this population,†the researchers report. They continue: “Aging is the primary risk factor associated with breast cancer development and mortality, resulting in a cumulative lifetime risk of 1 in 8 women developing the disease. Disease onset significantly impacts patient prognosis. While most cases are of late onset and occur in women over 50 years of age, early-onset BC is prevalent in certain populations and is associated with a poor prognosis and aggressive tumor behavior.â€Â
Data was collected and analyzed from May 2015 to December 2022, with the study population in Brazil spanning “27 municipalities in the southwest of Paraná, a region characterized by extensive pesticide use, predominantly rural work, and family farming, with significant participation from women,†the authors state. All patients included in the study underwent screening for familial cancer and genetic testing for BRCA 1 and 2 mutations. Â
Based on age and pesticide exposure, the women were organized into four groups: pesticide-unexposed women with early disease onset (48 women), pesticide-unexposed women with late disease onset (45 women), pesticide-exposed women with early disease onset (50 women), and pesticide-exposed women with late disease onset (45 women).Â
A variety of additional clinicopathological variables were considered, including menopausal status at diagnosis, body mass index, hormonal receptor status (estrogen and progesterone, positive or negative), human epidermal growth factor receptor 2 (HER2) overexpression, Ki67 proliferation index, histological grade, breast cancer molecular subtype, tumor size, presence of distant metastasis, lymph node metastasis, risk stratification for recurrence and death, chemoresistance, and death occurrence. Analyses were also performed to assess the relationship between cytokine levels, pesticide exposure, and disease onset age.Â
As a result, the researchers find that:Â Â
- the late-onset group shows a greater frequency of low-grade tumors in exposed patients compared to the unexposed group.  Â
- a higher frequency of high-risk stratification for recurrence and death is seen in early-onset patients when comparing exposed and unexposed groups.Â
- patients in the late-onset group show a higher frequency of triple-negative tumors than unexposed women.Â
- IL-12 levels are significantly lower in exposed patients in the early-onset group compared to unexposed patients in the same group. Â
- early-onset patients show positive correlation between cytokine levels and pesticide exposure while late-onset patients show negative correlations.Â
This study reveals “distinct cytokine profiles correlated with pesticide exposure depending on the age of disease onset. In early-onset patients, pesticide exposure positively correlated with IL-1ß, IL-17A, and IL-4 [ILs are interleukins, a class of glycoproteins, or cytokines, produced by leukocytes, or white blood cells, for regulating immune responses], while in late-onset patients, pesticide exposure showed a negative correlation with IL-12, IL-4, and IL-17A,†the authors share. According to the authors: “These findings suggest that young women exposed to pesticides tend to develop decreased serum levels of IL-12. This feature is possibly associated with reduced type I immunity which is important for eliminating BC. Type I immunity promotes natural killer cell (NK) and CD8+ T-cell-mediated tumor cytotoxicity and toxic mediator release by phagocytes within the tumor microenvironment, leading to cancer cell death via multiple mechanisms.â€Â
In examining the cytokine levels within each patient, an association between early-onset exposed women and the development of high-risk tumors was determined. “These findings indicate that pesticide exposure induces an inflammaging-like state in young women, with increased levels of systemic IL-1 and reduced levels of IL-12 contributing to the increased risk of severe disease in these individuals,†the researchers conclude.Â
Environmental exposure to pesticides affects the homeostasis of mammary epithelial cells and can result in cancer development. Pesticide exposure triggers inflammatory responses, which leads to the release of toxic mediators like reactive oxygen species (ROS). “These processes are linked to precarcinogenic events, which may result in cumulative mutations over time and genomic instability,†the authors say. They continue, “Environmental factors, particularly those encountered throughout life, can play a key role in influencing the natural history of mammary gland tumorigenesis and BC progression. Occupational pesticide exposure is a significant environmental risk factor for BC.â€Â Â
With greater female participation in rural labor comes an increase in women’s health risks with direct exposure to pesticides that significantly impacts mammary tissues and creates a pro-inflammatory environment. This is characterized by antioxidant depletion, elevated levels of tumor necrosis factor-alpha (TNFα), and increased activity of peroxisome proliferator-activated receptor gamma (PPARγ)—all contributing to cancer progression. Â
Many pesticides have been detected in women’s mammary gland tissues and breast milk. (See additional studies here and here.) The researchers postulate, “Approximately 35 pesticides with carcinogenic potential have been identified as contributors to tumors or other adverse effects on the mammary glands, indicating that exposure to these substances directly affects breast cells. Studies in animal models demonstrate that exposure to certain pesticides is linked to significant genetic damage, such as DNA breaks and aneuploidy—critical alterations that can lead to the development of breast cancer.â€Â
Scientific literature finds that pesticide exposure disrupts cellular homeostasis, causes cellular injury, and can lead to cell death. Exposure can also initiate the development of diseases by compromising immunosurveillance, particularly against tumors. (See studies here, here, and here.) The heightened risks for cancer development are associated with the cumulative genotoxic effects, chromosomal damage, and inflammation that occurs after pesticide exposure. These effects lead to genomic instability and immune alterations that have “significant implications for carcinogenesis and tumor progression,†the authors report.Â
Long-term oxidative stress is linked to many chronic diseases, including cancer, and there is a wide body of science showing many pesticides causing oxidative stress. (See here, here, and here.) Previous studies also link atrazine to breast cancer, as this pesticide can suppress systemic and local tumor immune functions that promote tumor development. Low concentrations of glyphosate, even with acute exposure, increase ROS levels, induce hypoxia, and disrupt the DNA repair response in human triple-negative BC cells. See more examples of studies on pesticides causing cancer here, here, here, here, here, and here.Â
As an alternative to chemicals that cause cancer, endocrine disruption, and a myriad of other health effects, organic agriculture provides a holistic solution for food production. In managing all land with organic methods, the crises of public health, biodiversity, and climate change are mitigated and the environment, and all organisms it supports, are protected. Â
Learn more about the health implications of pesticide exposure through the Pesticide-Induced Diseases Database, as well as the benefits of organic here and here. Stay up to date with the latest science and policy developments with the Daily News Blog and sign up to receive Action of the Week and Weekly News Updates straight to your inbox here. Â
All unattributed positions and opinions in this piece are those of Beyond Pesticides. Â
Source:Â
Cardoso Maciel Costa Silva, R. et al. (2024) Occupational exposure to pesticides affects systemic cytokine profile and correlates with poor clinical prognosis in young women with breast cancer, Immunopharmacology and Immunotoxicology. Available at: https://www.tandfonline.com/doi/abs/10.1080/08923973.2024.2430665. Â
