GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER

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DESCRIPTION (provided by applicant): Many polycyclic aromatic hydrocarbons (PAH) have carcinogenic potential through the formation of DNA adducts. Differences in PAH-DNA adduct levels between cancer cases and controls and between normal and tumor tissue has been demonstrated in breast and lung cancer. PAH exposures have been found associated with prostate cancer in epidemiologic studies, and DNA adducts have been detected in prostate tissue, but heretofore no effort has been made to link retrospective PAH exposures with the biomarker of PAH-DNA adducts in the prostate. We propose to retrospectively assess the main environmental sources of PAH exposures (e.g., diet, occupation, smoking) and potentially important intervening genetic factors in DNA adduct formation in 400 prostate cancer cases. These genetic factors include polymorphisms in xenobiotic metabolizing enzymes responsible for PAH activation and detoxification and DNA repair genes that can reverse PAH-DNA adduct formation. The proposed study will examine the importance of duration timing and type of PAH exposure, and test the effects of genetic and pathologic factors, in the formation DNA adducts in the prostate. Our proposed study design parallels work currently being done in breast cancer by study investigators, and these combined efforts are geared to offer a promising new line of investigation into the environmental etiology of hormonally-related cancers. The proposed study is a supplemental application to the NIEHS-flinded study, "Gene-Environment Interaction in Prostate Cancer" (5 ROl ES 011126-02) and will utilize the study population that is be enrolled in this study. Our results will provide researchers with a framework to conduct multi-level (e.g., environmental, genetic, biologic) risk assessment in prostate and related cancers where PAH are thought to play a major role in the carcinogenesis pathway.