DETERMINANTS OF STEROID HORMONES IN BLACK AND WHITE MEN

各种各样的证据表明，长期暴露于高水平的内源性雄激素会增加患前列腺癌的风险。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基因的多态性也与前列腺癌的风险有关。这些生活方式和遗传因素对前列腺癌病因的影响可以通过类固醇激素水平或代谢的改变介导，至少部分介导。然而，在男性中观察到的激素水平的巨大个体间差异的原因尚未得到充分的研究。该项目的主要目的是通过纵向分析，评估631名黑人和873名白人男性（年轻）成人冠状动脉风险发展（CARDIA）研究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。基线数据从1985-86年的CARDIA队列中收集，随后在第2、5、7和10年进行随访检查。在拟议的项目中，将使用先前收集和储存的在二年级、七年级和十年级后续检查中获得的血清样本，以及五年级检查中获得的DNA样本。具体来说，将比较非裔美国人和白人男性8年血清类固醇激素浓度的纵向变化。肥胖、饮食和体育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将被检查。此外，我们将评估血清雄激素水平与雄激素受体基因CAG重复长度之间的关系，并探索性分析5- α -还原酶基因多态性与血清3 -雄甾二醇葡萄糖醛酸水平之间的关系，3 -雄甾二醇葡萄糖醛酸是5- α -还原酶活性的潜在表型标志物。本研究的结果将首次提供双种族人群中类固醇激素变化及其相关性的纵向分析。

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.