Determinants of Steroid Hormones in Black and White Men

描述（由申请人提供）：性激素和胰岛素样生长因子（IGF）系统的组分似乎在前列腺癌病因学中起重要作用。然而，研究血液雄激素浓度和参与雄激素生物合成的遗传多态性与前列腺癌风险相关性的流行病学研究结果并不一致。这种不一致至少部分归因于与准确表征血清激素水平相关的方法学问题。尽管IGF-1和前列腺癌风险之间的正相关性的一致观察，在成人血清IGF水平的决定因素还没有得到很好的理解。因此，需要进行大型研究，以评估不同种族/民族群体中循环性激素和IGF浓度的生活方式和遗传决定因素，以更好地了解这些因素之间的相互关系。（年轻）成人冠状动脉风险发展（CARDIA）男性激素研究（CMHS）旨在评估生活方式和遗传因素与年轻成年黑人和白色男性血清雄激素和IGF浓度的纵向关联。作为CMHS的一部分，在8年时间内连续收集624名黑人和796名白色男性的血清样本，测量3 α-雄甾烷葡糖苷酸（AAG）、IGF-1、IGF结合蛋白-3（IGFBP-3）和性激素结合球蛋白（SHBG）的浓度，这些男性在首次激素测量时年龄为20-34岁。对于这种竞争性更新申请，我们建议通过将我们的调查集中在四个候选基因多态性（即，SRD 5A 2 V89 L、IGF-1 CA重复长度、IGFBP-3 A/C和SHBG TAAAA重复长度）与血清AAG、IGF-1、IGFBP-3和SHBG浓度在563名黑人和762名白色男性中进行比较。这些多态性是根据其潜在的功能意义来选择的。CMHS是唯一适合解决这些协会，因为大样本量的黑人和白色男性包括在研究中，成本效益利用现有的激素，生长因子和生活方式的数据异常高的细节和质量，并纳入激素水平和生活方式因素的重复测量超过8年。

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.