ANDROGEN PATHWAY POLYMORPHISMS AND PROSTATE CANCER RISK

描述：（改编自申请人摘要）。 它已成为 越来越明显的是，有一个强大的继承组成部分， PC的风险 病例对照研究表明，男性近亲 PC可能有2.5倍的风险。 继承遗产的男人 异常乳腺癌（BRCA 1）基因，使女性易患乳腺癌 和卵巢癌，似乎有PC的风险增加。 此外，本发明还提供了一种方法， 一些罕见的没有BRCA 1的家庭已经被确定， 是一个常染色体显性基因赋予PC的高风险。 即使加在一起， 这些罕见的家族性PC不太可能包含超过一个小的 PC的遗传形式的一部分。 正常和癌变前列腺的细胞都高度响应于 雄激素的作用;代谢的个体间差异 雄激素可能会影响PC的发展。 遗传 对雄激素反应的差异可以解释部分遗传性 这种癌症的风险。 因此，这些研究将测试 一个或多个AR基因产生改变的雄激素的假说 代谢，从而增加PC的风险。 一个小的结果 AR基因多态性的病例对照研究与此一致 假说. 由于AR多态性的频率基本上是 在非裔美国人中，这种机制也可以解释 非裔美国人中PC的发病率较高。 这些计划包括 类固醇还原酶和AR多态性频率的评估 基因，使用来自150名PC患者和150名对照男性的血液样本 年龄和种族都匹配

DESCRIPTION: (Adapted from Applicant's Abstract). It has become increasingly evident that there exists a strong inherited component to the risk of PC. Case-control studies have indicated that close relatives of men with PC may have a 2.5-fold excess risk of this disease. Men who inherit the abnormal breast cancer (BRCA1) gene, that predisposes women to breast and ovarian cancer, appear to have an increased risk of PC. In addition, some rare families that do not have BRCA1 have been identified where there is an autosomal dominant gene conferring a high risk of PC. Even combined, these rare familial forms of PC are unlikely to comprise more than a small fraction of the inherited forms of PC. The cells of both the normal and cancerous prostate are highly responsive to the effects of androgens; inter-individual differences in the metabolism of androgens can be expected to affect the development of PC. Genetic differences in response to androgens may explain a portion of the inherited risk for this cancer. For this reason, these studies will test the hypothesis that one or more of the AR genes produces altered androgen metabolism and thereby increases the risk of PC. The results of a small case-control study of the AR gene polymorphism are consistent with this hypothesis. Since the frequency of the AR polymorphisms is substantially higher in the African American population, this mechanism could also explain the higher incidence of PC in African American men. The plans include assessment of the frequency of polymorphisms in the steroid reductase and AR genes, using blood samples from 150 patients with PC and 150 control men matched for age and race.