Determinants of Steroid Hormones in Black and White Men

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DESCRIPTION (provided by applicant): Sex hormones and components of the insulin-like growth factor (IGF) system appear to play important roles in prostate cancer etiology. However, results of epidemiologic studies that examined associations of blood androgen concentrations, and genetic polymorphisms involved in androgen biosynthesis with prostate cancer risk are inconsistent. At least part of this inconsistency has been attributed to methodologic issues related to accurately characterizing serum hormone levels. Despite consistent observations of a positive association between IGF-1 and prostate cancer risk, the determinants serum IGF levels in adults in not well understood. Thus, large studies are needed to assess lifestyle and genetic determinants of circulating sex hormone and IGF concentrations in various racial/ethnic groups to better understand the interrelationships among these factors. The Coronary Artery Risk Development in (Young) Adults (CARDIA) Male Hormone Study (CMHS) is designed to evaluate longitudinal associations of lifestyle and genetic factors with serum androgen and IGF concentrations in young adult black and white men. As part of the CMHS, concentrations of 3alpha-androstanediol glucuronide (AAG), IGF-1, IGF binding protein-3 (IGFBP-3), and sex hormone binding globulin (SHBG) were measured in serially collected serum samples over an eight-year period from 624 black and 796 white men who were aged 20-34 years at the time of the first hormone measurement. For this competitive renewal application, we propose to expand on previous CMHS objectives by focusing our investigations on associations of four candidate gene polymorphisms (i.e., SRD5A2 V89L, IGF-1 CA repeat length, IGFBP-3 A/C, and SHBG TAAAA repeat length) with serum AAG, IGF-1, IGFBP-3 and SHBG concentrations among the 563 black and 762 white men for whom DNA is available. These polymorphisms were selected based on their potential functional significance. The CMHS is uniquely suited to address these associations because of the large sample size of black and white men included in the study, the cost-effective utilization of existing hormone, growth factor and lifestyle data of unusually high detail and quality, and the incorporation of repeated measures of both hormone levels and lifestyle factors over 8-years.