Genetic Analysis of Hereditary Prostate Cancer Families

遗传性前列腺癌家族的基因分析

• 批准号: 6781330
• 负责人: KATHLEEN A COONEY
• 金额: $ 32.85万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6781330
• 关键词: brca gene; cancer risk; clinical research; family genetics; gel electrophoresis; gene expression; genetic markers; genetic registry /resource /referral center; genetic screening; genetic susceptibility; genotype; high performance liquid chromatography; histopathology; human subject; linkage mapping; loss of heterozygosity; male; molecular biology information system; neoplasm /cancer genetics; prostate neoplasms; tumor suppressor genes

DESCRIPTION (provided by applicant): The recognition that prostate cancer clusters within families has led many research teams including our own to collect families with multiple cases of prostate cancer for linkage studies. Unfortunately, despite the collection and analysis of a large number of such families, the major genes that contribute to inherit prostate cancer susceptibility have been difficult to fully characterize. At least eight loci have been proposed and further studies are now required to determine the most clinically important prostate cancer predisposition genes. The University of Michigan Prostate Cancer Genetics Project (PCGP) was established in 1995 as a family based study of inherited prostate cancer susceptibility. A genome wide linkage scans was recently completed using 176 multiplex PCGP families, which has implicated several new genomic regions for additional study. The strongest evidence for prostate cancer linkage was on chromosome 17 adjacent to the BRCA1 gene. Mutations in the BRCA1 gene have been shown to increase the risk of breast and ovarian cancer in women as well as prostate cancer in men, however BRCA1 mutations have not been previously identified in prostate cancer families. To further characterize the role of BRCA1 in hereditary prostate cancer and to define other prostate cancer susceptibility genes and their associated clinical syndromes, the following three Specific Aims are proposed: 1) To evaluate the role of the breast cancer gene BRCA1 as a prostate cancer susceptibility gene in PCGP families, 2) to localize and characterize candidate prostate cancer susceptibility genes in PCGP families, 3) To identify prostate cancer susceptibility genes that specifically influences the risk of developing clinically aggressive prostate cancer. Completion of these aims will improve our understanding of the genes that predispose men to prostate cancer as well as the clinical syndromes associated with specific gene mutations. Ultimately, this information may have clinical utility to identify those men at highest risk of prostate cancer who may benefit from early detection and/or chemoprevention strategies.

描述（由申请人提供）：认识到前列腺癌在家庭内聚集，导致包括我们自己在内的许多研究团队收集患有多个前列腺癌病例的家庭进行关联研究。不幸的是，尽管收集和分析了大量此类家族，但导致遗传性前列腺癌易感性的主要基因仍难以完全表征。已提出至少八个基因座，现在需要进一步研究以确定临床上最重要的前列腺癌易感基因。 密歇根大学前列腺癌遗传学项目 (PCGP) 成立于 1995 年，是一项基于家庭的遗传性前列腺癌易感性研究。最近使用 176 个多重 PCGP 家族完成了全基因组连锁扫描，这暗示了几个新的基因组区域需要进一步研究。前列腺癌连锁的最有力证据位于与 BRCA1 基因相邻的 17 号染色体上。 BRCA1 基因突变已被证明会增加女性患乳腺癌和卵巢癌以及男性患前列腺癌的风险，但此前尚未在前列腺癌家族中发现 BRCA1 突变。 为了进一步表征 BRCA1 在遗传性前列腺癌中的作用并定义其他前列腺癌易感基因及其相关的临床综合征，提出以下三个具体目标： 1) 评估乳腺癌基因 BRCA1 作为 PCGP 家族中前列腺癌易感基因的作用，2) 定位和表征 PCGP 家族中候选前列腺癌易感基因，3) 鉴定特异性影响风险的前列腺癌易感基因发展为临床侵袭性前列腺癌。完成这些目标将提高我们对男性易患前列腺癌的基因以及与特定基因突变相关的临床综合征的了解。最终，这些信息可能具有临床实用性，可以识别那些前列腺癌风险最高的男性，他们可以从早期检测和/或化学预防策略中受益。