Epigenetic markers for pesticide exposure and cancer risk
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Non-technical overview of the research topic and relevance to breast cancer: Pesticides, including insecticides and herbicides (weed killers), pose a threat to human health. Organophosphate pesticides (OPs) are the most commonly used insecticides in the U.S., and glyphosate is the most commonly used herbicide. The proposed project focuses on identifying biomarkers for exposures to these two types of pesticides. A few studies have shown that exposure to OPs and glyphosates may be associated with increased breast cancer risk in humans and that they increase cell division and disrupt hormone signaling in breast cancer cells and animal models. However, additional studies are needed to determine if exposure to these pesticides increase breast cancer risk in humans. Research question(s) or central hypotheses: We hypothesize that methylation in blood cell DNA is associated with urinary measures of OP and glyphosate exposure, and that some sites of DNA methylation will be identified that can serve as biomarkers for the exposures. Given that OPs and glyphosates disrupt hormone signaling, we also hypothesize that the biomarkers will be associated with known hormone-related breast cancer risk factors like breast density and age at menopause, which would increase our understanding of how DNA methylation relates to breast cancer development. General methodology: 400 women from the UCI Athena Breast Health Network, a cohort of &gt;7,000 breast screening patients at UC Irvine who agreed to participate in research, will be recruited to participate in the study, which includes filling out study surveys and donating a blood sample and two urine samples. Study participants will be offered a personalized report containing their urinary levels of OP metabolites and glyphosate in comparison to national averages and averages among the study cohort, as well as access to the study physician if they have any questions about their report or their breast cancer risk. Methylation arrays will be used to determine methylation levels at &gt;850,000 DNA sites, and the sites that are most correlated with urinary levels of OP metabolites and glyphosate will be identified as biomarkers for OP and glyphosate exposure. Innovative elements: This study has the potential to transform the field of breast cancer research related to environmental exposures because the DNA methylation markers will allow for more cost-effective, large scale analysis of samples collected in prospective studies as well as previously established cohorts in order to elucidate the relationship between the most commonly used pesticides in the U.S. and breast cancer risk, which may lead to changes in policy regarding use of these pesticides in order to protect human health. A better understanding of whether these pesticides affect breast cancer risk may help women make more informed decisions regarding pesticide exposures for herself and her loved ones. We will use the most up-to-date methylation array to analyze &gt;850,000 DNA sites, the most sites out of all arrays currently available. Previous array analyses which analyzed fewer sites led to numerous discoveries of specific sites of DNA methylation being associated with various aspects of human health, including smoking status, and we anticipate that this new array will enable the discovery and validation of a statistically significant panel of methylation markers associated with pesticide exposure. Advocacy involvement and relevance to the human issues associated with breast cancer: Three experienced breast cancer research advocates comprise my Advocate Team for this study. They helped in the development of the specific aims, including the decision of which pesticides to study, and in development of the recruitment strategy. The protocol and all participant-facing materials will be vetted by the Advocate Team before implementation. The proposed study is extremely relevant to women who are eager to know about their breast cancer risk, especially those risk factors that can be avoided. There is suspicion among many women about the relationship between pesticides and breast cancer risk. The proposed study would help clarify this relationship.