PCBs, CYP1A1 Polymorphism and Breast Cancer Risk in CT

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(Revised Abstract) DESCRIPTION: Polychlorinated biphenyls (PCBs) are potent environmental endocrine disruptors. They are also strong inducers of key genes involved in steroid metabolism and xenobiotic metabolism, such as human cytochrome CYP1A1. Recent epidemiological studies suggest that women are at increased risk of breast cancer if they have an elevated body burden of PCBs and a CYP1A1 m2 genotype. Toxicological studies support these findings by showing that PCBs induce CYP1A1 to metabolize environmental carcinogens into highly reactive intermediates resulting in DNA damage and ultimately carcinogenesis. Due to the widespread exposure to PCBs and the important role of CYP1A1 in carcinogen activation and steroid hormone metabolism, there exists an urgent need to study the relationship between PCBs, the CYP1A1 genotype and breast cancer risk. Against this background, a case-control study of body burden of PCBs, CYP1A1 genetic polymorphisms and breast cancer risk is proposed in Connecticut, one of the areas with the highest incidence rates of breast cancer in the United States. The primary aim of this study is to test the hypothesis that women with an elevated body burden of PCBs and with specific CYP1A1 genotypes have an increased risk of breast cancer. The blood samples used to determine CYP1A1 genotypes for the case-control study will come from a recently completed breast cancer case-control study in Connecticut, which has recruited 475 incident breast cancer cases and 502 controls. Information on environmental exposures and potential confounding factors has already been collected and blood serum samples were analyzed for PCBs and DDE through the aforementioned parent breast cancer case-control study. Use of existing blood samples and environmental exposure data collected by the parent breast cancer study provide cost efficiency to the study.