A prospective follow-up study of pesticide exposure, dietary intakes, and genetic polymorphisms and the risk of prostate cancer.

摘要

Background. Prostate cancer is the most common cancer in men in the United States and the second most common cause of cancer death. Despite these trends, there are only three established risk factors for prostate cancer, increasing age, race/ethnicity, and family history. The use of large, well designed prospective studies may help to elucidate additional lifestyle, environmental and genetic risk factors for this disease.;Methods. This dissertation contains three separate studies that examine risk factors for prostate cancer. The first study is a prospective cohort analysis of the relationship between the organophosphate insecticide, dichlorvos, and risk of prostate cancer. The cohort consists of 57,311 licensed pesticide applicators that have been followed for cancer development since 1993. The second study uses the same cohort and evaluates the association between meat types, meat cooking methods, meat doneness, and meat mutagens and the risk of prostate cancer among 23,080 men with complete dietary data. The third study investigates the interaction of dietary heterocyclic amine intake and xenobiotic metabolizing gene variants and risk of prostate cancer using a nested case-control design among 2,253 participants enrolled in a genome-wide association scan of prostate cancer.;Results. Study One: We did not find an association between dichlorvos exposure and prostate cancer. Some elevated risks were apparent among those with a family history of prostate cancer however these results were based on small numbers. Study Two: We found no association between meat type or specific cooking method and prostate cancer risk. However, intake of well or very well done total meat was associated with an increased risk of incident and advanced prostate cancer. Study Three: Variants in several glutathione S-transferase loci may modify the association between heterocyclic amine intake and prostate cancer.;Conclusions. Family history of prostate cancer may mediate the risk between dichlorvos exposure and prostate cancer. Intake of well and very well done meat is associated with an increased risk for prostate cancer. Variants in low-penetrance genes likely interact with dietary intakes of heterocyclic amines to alter prostate cancer risk.