INVESTIGATING THE INFLUENCE OF ENVIRONMENTAL CHEMICAL EXPOSURE ON BREAST CANCER RISK

Breast cancer is a common malignancy that is known to be influenced by an individual’s environment. While recent progress has been made in evaluating environmental chemicals for breast cancer risk, further efforts are needed to prioritize and screen the immense scope of chemicals understudied with respect to this disease outcome. Additionally, significant data gaps exist surrounding chemicals in the household that may be associated with breast cancer risk, as well as cancer related biological mechanisms that may be perturbed as a result of exposure to specific substances.This dissertation integrates exposure science, toxicology, epidemiology, and data science approaches to investigate the influence of environmental chemical exposure on breast cancer risk. First, understudied chemicals likely impacting breast cancer risk that occur as mixtures in household environments were characterized using database-driven approaches. Second, differences in household chemical abundances for women with and without breast cancer were evaluated leveraging non-targeted analysis of dust wipes samples from a breast cancer cohort. Chemical abundances were then linked to self-reported exposure data using advanced data analytics techniques. Third, mechanisms of environmental exposure-induced breast cancer were informed through in vitro high-throughput screening approaches coupled with machine learning, and understudied chemicals that perturb these mechanisms were identified.In conclusion, this dissertation highlights the following findings: (1) high-throughput and data science approaches are useful for chemical characterization and prioritization efforts focused on breast cancer, (2) endocrine disruptors, pesticides, and dyes commonly appeared across analyses as chemicals of concern, and (3) personal care product usage was linked to exposure of chemicals associated with increased breast cancer risk.