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)系统的组成部分似乎在前列腺癌的病因中扮演着重要的角色。然而，检测血液雄激素浓度和雄激素生物合成所涉及的基因多态与前列腺癌风险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描述血清激素水平有关的方法学问题。尽管一致地观察到IGF-1与前列腺癌风险呈正相关，但成人血清IGF水平的决定因素尚不清楚。因此，需要进行大规模研究，以评估不同种族/民族的生活方式和循环性激素和IGF浓度的遗传决定因素，以更好地了解这些因素之间的相互关系。青年成人冠状动脉风险发展(CARDIA)男性激素研究(CMHS)旨在评估年轻成年黑人和白人男性的生活方式和遗传因素与血清雄激素和IGF浓度的纵向关联。作为CMHS的一部分，在连续收集的624名黑人和796名白人男性的血清样本中，测定了3α-雄烷二醇葡萄糖醛酸(AAG)、IGF-1、IGF结合蛋白-3(IGFBP-3)和性激素结合球蛋白(SHBG)的浓度。对于这一竞争性更新应用，我们建议扩展之前的CMHS目标，重点研究在563名黑人和762名白人男性中，四个候选基因多态(即SRD5A2 V89L、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浓度的关系。这些多态是根据它们潜在的功能意义进行选择的。CMHS特别适合于解决这些关联，因为这项研究包括了大量黑人和白人男性样本，对现有荷尔蒙、生长因子和生活方式数据的成本效益利用异常详细和高质量，并纳入了8年来对荷尔蒙水平和生活方式因素的重复测量。

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.