GENETIC ANALYSIS OF HEREDITARY PROSTATE CANCER FAMILIES

描述：（改编自研究者摘要）前列腺癌是 最常见的癌症原因和癌症死亡的第二大原因， 美国男人虽然与年龄和种族密切相关，但家庭 病史也被证明是前列腺癌的重要决定因素 风险相关风险的大小似乎取决于 患前列腺癌的家庭成员人数和年龄 发病于受影响的家庭成员。高密度遗传连锁研究 前列腺癌家族导致了第一个 前列腺癌易感基因，HPC 1，定位于1 q24 -25。外加剂 测试表明，该位点可能有助于前列腺癌的易感性， 在不到三分之一的高密度前列腺癌家族中。复制 研究显示前列腺癌与此相关的证据不一致， 我们使用非参数连锁方法对59个家庭进行了分析， 为HPC 1的存在提供了最有力的支持。在过去六 几个月后，又提出了两个额外的前列腺癌易感基因： 1q42.2-43处的HPC 2和Xq 29 -28处的HPCX;这些基因座的独立验证 还没有报道。 为了进一步支持HPC 1对一个显著的 部分遗传性前列腺癌病例，并确定其他的作用 提出的易感基因座，包括HPC 2和HPCX，及其相关的 临床综合征，提出以下具体目标：1.）审查 与HPC 1相关的前列腺癌家族的特征， 其他HPC基因座，以确定独特的组织病理学和临床特征， 这些家庭; 2。继续确定HPC 1在遗传中的作用， 前列腺癌;和3.）评估其他潜在HPC的贡献 遗传性前列腺癌的基因，包括HPC 2在1q42.2-43和HPCX在 XQ27-28这些研究将有助于我们更好地理解 前列腺癌易感基因及其相关临床综合征。

DESCRIPTION: (Adapted from the Investigator's Abstract) Prostate cancer is the most common cause of cancer and the second leading cause of cancer deaths in American men. Although most strongly correlated with age and race, family history has also been shown to be an important determinant of prostate cancer risk. The magnitude of the associated risk appears to be dependent upon the number of family members with prostate cancer and the age of prostate cancer onset in affected family members. Genetic linkage studies of high-density prostate cancer families have resulted in the localization of the first prostate cancer susceptibility gene, HPC1, which maps to 1q24-25. Admixture tests suggest that this locus may contribute to prostate cancer susceptibility in less than one-third of high-density prostate cancer families. Replication studies have revealed inconsistent evidence of prostate cancer linkage to this locus; our analysis of 59 families using nonparametric linkage methods has provided the strongest support for the existence of HPC1. In the past six months, two additional prostate cancer susceptibility genes have been proposed: HPC2 at 1q42.2-43 and HPCX at Xq29-28; independent verification of these loci has not been reported. To further support the hypothesis that HPC1 contributes to a significant fraction of hereditary prostate cancer cases and to define the role of other proposed susceptibility loci, including HPC2 and HPCX, and their associated clinical syndromes, the following Specific Aims are proposed: 1.) to examine the characteristics of prostate cancer families that are linked to HPC1 and other HPC loci to determine unique histopathological and clinical features of these families; 2.) to continue to define the role of HPC1 in hereditary prostate cancer; and 3.) to assess the contribution of other potential HPC genes to hereditary prostate cancer, including HPC2 at 1q42.2-43 and HPCX at Xq27-28. These studies will lead to improvements in our understanding of prostate cancer predisposition genes and their associated clinical syndromes.