DESCRIPTION (provided by applicant): Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Prostate cancer etiology remains elusive but there is growing evidence that dietary patterns are associated with prostate carcinogenesis. The most consistent dietary finding is that diets high in fat or high-fat foods increase risk and there is increasing evidence that compounds found in vegetables (e.g., lycopene, glucosinolates) decrease risk. However, results are not consistent across studies and there is no scientific consensus for specific dietary recommendations to reduce prostate cancer risk. Non-dietary factors associated with risk include age, race and family history. These and other risk factors may interact with dietary components and alter the prooxidant-antioxidant balance in the prostate. This proposal is for a comprehensive investigation into the associations of dietary fat, fruit and vegetable intakes and polymorphisms in genes that encode oxidative stress regulatory enzymes with the risk of prostate cancer. Our hypothesis is that dietary and other factors that increase oxidative stress (e.g., dietary fat, smoking) are associated with increased risk of prostate cancer; dietary factors that decrease oxidative stress are associated with decreased risk of prostate cancer; and the magnitude of these risks will vary by cancer susceptibility genetic profile. We will test whether polymorphisms in genes whose products affect tissue responses to oxidative stress influence prostate cancer risk, and whether there are interactions of these polymorphisms with dietary factors related to oxidative stress. Our study sample is the 12,025 male participants in CARET (The Beta-Carotene and Retinol Efficacy Trial). To date, there are 718 confirmed cases of primary prostatic carcinoma. This proposed study will provide important information about prostate cancer etiology and suggest new strategies for prevention and control.
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