ANDROGEN PATHWAY POLYMORPHISMS AND PROSTATE CANCER RISK

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DESCRIPTION: (Adapted from Applicant's Abstract). It has become increasingly evident that there exists a strong inherited component to the risk of PC. Case-control studies have indicated that close relatives of men with PC may have a 2.5-fold excess risk of this disease. Men who inherit the abnormal breast cancer (BRCA1) gene, that predisposes women to breast and ovarian cancer, appear to have an increased risk of PC. In addition, some rare families that do not have BRCA1 have been identified where there is an autosomal dominant gene conferring a high risk of PC. Even combined, these rare familial forms of PC are unlikely to comprise more than a small fraction of the inherited forms of PC. The cells of both the normal and cancerous prostate are highly responsive to the effects of androgens; inter-individual differences in the metabolism of androgens can be expected to affect the development of PC. Genetic differences in response to androgens may explain a portion of the inherited risk for this cancer. For this reason, these studies will test the hypothesis that one or more of the AR genes produces altered androgen metabolism and thereby increases the risk of PC. The results of a small case-control study of the AR gene polymorphism are consistent with this hypothesis. Since the frequency of the AR polymorphisms is substantially higher in the African American population, this mechanism could also explain the higher incidence of PC in African American men. The plans include assessment of the frequency of polymorphisms in the steroid reductase and AR genes, using blood samples from 150 patients with PC and 150 control men matched for age and race.