5 ALPHA REDUCTASE GENOTYPE, RACE PROSTATE CANCER RISK

5 α还原酶基因型，种族前列腺癌风险

• 批准号: 2908927
• 负责人: JUERGEN K REICHARDT
• 金额: $ 37.46万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2908927
• 关键词: African American; Asian Americans; androstane compound; cancer risk; clinical research; enzyme activity; gene mutation; genetic polymorphism; genetic susceptibility; genotype; human genetic material tag; human subject; male; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplastic process; nucleic acid sequence; prostate neoplasms; racial /ethnic difference; steroid hormone metabolism; testosterone; testosterone 5 alpha reductase

DESCRIPTION: (Adapted from the Investigator's Abstract) Prostate cancer is currently the most common cancer among American men. Regulation of prostatic cell growth is largely controlled by androgens including especially dihydrotestosterone (DHT). This compound is synthesized from the male hormone testosterone by the enzyme 5-alpha reductase which is encoded in the prostate by the SRD5A2 gene. The etiology of prostate cancer appears to include increased steroid 5-alpha reductase activity particularly across racial/ethnic groups which are at very different risk for prostate cancer, such as high-risk African-Americans and lower risk Asians, the two extreme groups for risk. We have identified and characterized genetic variability in the SRD5A2 gene among various racial/ethnic groups in the US and between prostate cancer cases and controls. These investigations made use of a large multiethnic cohort in Los Angeles and Hawaii. We propose to build on and expand our studies of the SRD5A2 gene and prostate cancer by epidemiologic, genetic and biochemical methods. It is our overall hypothesis that genetic variation at the SRD5A2 locus plays a significant role in predisposition to and progression of prostate cancer and in explaining the racial/ethnic variation of risk. To this end, we intend to investigate the following interrelated six specific aims: 1) To identify all constitutional ("germline") DNA variations across the entire SRD5A2 gene that might contribute to predisposition to prostate cancer; 2) To determine the relationship between each variant identified in Specific Aim 1 to prostate cancer risk in for racial/ethnic populations: 4) To identify somatic mutations in the SRD5A2 gene involved in prostate cancer progression; 5) To characterize the biochemical properties of the somatic DNA genetic variants identified in Specific aims 1 and 4 in an in vitro model system; 6) To determine the contribution of somatic DNA genetic variants in the SRD5A2 gene to prostate cancer progression within and across racial/ethnic groups. Therefore, we will investigate the molecular basis of predisposition to prostate cancer and its progression in a multidisciplinary study rooted in molecular epidemiology with significant implications for presymptomatic identification of at-risk individuals, targeted chemoprevention and improved treatment of this disease.

描述：（改编自研究者摘要）前列腺癌是 目前是美国男性中最常见的癌症。前列腺调节 细胞生长主要由雄激素控制， 双氢睾酮（DHT）。这种化合物是由雄性激素 睾丸激素由前列腺中编码的酶5-α还原酶 SRD 5A 2基因。前列腺癌的病因似乎包括 增加类固醇5-α还原酶活性，特别是在种族/民族之间 患前列腺癌的风险差异很大的人群，如高风险人群， 非裔美国人和低风险的亚洲人，两个极端的风险群体。我们 已经确定并表征了SRD 5A 2基因的遗传变异性， 美国的各种种族/族裔群体以及前列腺癌病例和 对照这些调查利用了洛杉矶的一个大型多种族队列， 洛杉矶和夏威夷。我们建议建立和扩大我们的研究SRD 5A 2 基因和前列腺癌的流行病学，遗传学和生化方法。它 我们的总体假设是，SRD 5A 2基因座的遗传变异在 在前列腺癌的易感性和进展中以及在 解释风险的种族/民族差异。为此，我们打算 研究以下六个相互关联的具体目标：1）确定所有 在整个SRD 5A 2基因上的构成（“种系”）DNA变异， 可能导致前列腺癌的易感性; 2）为了确定 特定目标1中确定的每个变体与前列腺 种族/民族人群的癌症风险：4）识别体细胞突变 在参与前列腺癌进展的SRD 5A 2基因中; 5）表征 鉴定的体细胞DNA遗传变异的生化特性， 具体目标1和4在体外模型系统中; 6）为了确定 SRD 5A 2基因体细胞DNA遗传变异对前列腺增生的作用 在种族/族裔群体内和跨种族/族裔群体的癌症进展。所以我们会 研究前列腺癌易感性的分子基础及其 一项植根于分子流行病学的多学科研究的进展， 症状前识别风险的重要意义 个体，有针对性的化学预防和改善这种疾病的治疗。