DETERMINANTS OF STEROID HORMONES IN BLACK AND WHITE MEN

大量证据表明，长期接触高水平的内源性雄激素会增加罹患前列腺癌的风险。此外，非裔美国人的血统、高脂肪饮食、肥胖、缺乏运动和雄激素受体编码基因的多态性也与前列腺癌风险有关。这些生活方式和遗传因素对前列腺癌病因的影响可能至少部分是通过类固醇激素水平或代谢的变化来调节的。然而，在男性中观察到的荷尔蒙水平在个体间的巨大差异的原因还没有得到充分的研究。拟议项目的主要目标是在纵向分析中评估青年冠状动脉风险发展(CARDIA)研究中631名黑人和873名白人男性参与者的生活方式和血清类固醇激素和结合蛋白水平的遗传决定因素。基线数据收集自1985-86年的CARDIA队列，随后的后续检查在第2、5、7和10年进行。对于拟议的项目，将使用以前在第2、7和10年的后续检查中收集和存储的血清样本，以及第5年检查的DNA样本。具体地说，将比较非裔美国人和白人男性八年来血清类固醇激素浓度的纵向变化。我们将考察肥胖、饮食和体力活动等潜在可改变因素的变化对类固醇激素水平纵向变化的独立影响。此外，我们还将评估血清雄激素水平与雄激素受体基因CAG重复长度的关系，并对5-α-还原酶基因多态性与血清3a-雄烯二醇葡萄糖醛酸苷水平的关系进行探索性分析，3a-雄烯二醇葡萄糖醛酸苷是5-α-还原酶活性的潜在表型标记。这项研究的结果将首次对类固醇激素的变化及其在混血人群中的相关性进行纵向分析。

A diverse body of evidence suggests that long-term exposure to elevated levels of endogenous androgenic hormones increases the risk of prostate cancer. Moreover, African-American ancestry, a high- fat diet, obesity, physical inactivity and polymorphisms in the gene encoding the androgen receptor also have been linked to prostate cancer risk. The effect of these lifestyle and genetic factors on prostate cancer etiology could be mediated, at least partly, through alterations in steroid hormone levels or metabolism. However, reasons for the substantial inter- individual variation in hormone levels observed among men have not been adequately studied. The primary objective of the proposed project is to evaluate, in longitudinal analyses, lifestyle and genetic determinants of serum steroid hormone and binding protein levels in 631 black and 873 white male participants of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Study. Baseline data were collected from the CARDIA cohort in 1985-86, and subsequent Follow-up examinations occurred at Years 2, 5, 7, and 10. For the proposed project, previously collected and stored serum samples obtained at the Years 2, 7 and 10 follow-up exams, and DNA samples from the Year 5 exams will be utilized. Specifically, eight-year longitudinal changes in serum concentrations of steroid hormones will be compared between African- American and white men. Independent effects of changes in potentially modifiable factors such as obesity, diet and physical activity on longitudinal changes in steroid hormone levels will be examined. In addition, we will evaluate associations between serum androgen levels and CAG repeat length in the androgen receptor gene, and conduct exploratory analyses of the relation between polymorphisms in the gene for 5-alpha- reductase and serum levels of 3a-androstanediol glucuronide, a potential phenotypic marker of 5-alpha-reductase activity. Results of this study will provide the first longitudinal analyses of steroid hormone changes and their correlated in a bi-racial population.