ANDROGEN PATHWAY POLYMORPHISMS AND PROSTATE CANCER RISK

雄激素途径多态性与前列腺癌风险

• 批准号: 2010856
• 负责人: WILLIAM D HENNER
• 金额: $ 7.34万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-05 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2010856
• 关键词: age difference; androgen receptor; androgens; autosomal dominant trait; cancer risk; clinical research; disease /disorder etiology; family genetics; genetic polymorphism; human genetic material tag; human subject; hydrocarbon oxidoreductase; male; neoplasm /cancer genetics; prostate neoplasms; racial /ethnic difference; steroid hormone metabolism

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.

描述：(改编自申请人摘要)。它已经变成了 越来越明显的是，存在一个强大的继承组件 PC的风险。病例对照研究表明，男性的近亲 患有PC的人患这种疾病的风险可能是普通人的2.5倍。继承遗产的男人 异常乳腺癌(BRCA1)基因，使女性易患乳房 和卵巢癌，似乎有更高的风险PC。此外, 一些罕见的没有BRCA1基因的家系已经被发现 是一种常染色体显性遗传基因，具有PC的高风险。即使加在一起， 这些罕见的家族性PC不太可能包括超过一小部分 PC遗传形式的一部分。 正常前列腺癌和前列腺癌的细胞都对 雄激素的作用；雄激素代谢的个体差异 雄激素可以预期影响PC的发展。遗传 对雄激素反应的不同可能解释了部分遗传性 患上这种癌症的风险。出于这个原因，这些研究将测试 一种或多种AR基因产生改变的雄激素的假说 新陈代谢，从而增加患PC的风险。结果是一个小小的 AR基因多态性的病例对照研究与此一致 假设。由于AR多态的频率基本上是 在非裔美国人中，这一机制也可以解释 非洲裔美国男性的PC发病率较高。这些计划包括 类固醇还原酶和AR基因多态频率的评估 基因，使用150名PC患者和150名对照组的血液样本 年龄和种族都很匹配。