GENETIC ANALYSIS OF HEREDITARY PROSTATE CANCER FAMILIES

描述：(改编自《调查人员摘要》)前列腺癌是 年最常见的癌症原因和第二大癌症死亡原因 美国男人。尽管与年龄和种族最相关的是家庭 病史也被证明是前列腺癌的一个重要决定因素。 风险。相关风险的大小似乎取决于 前列腺癌家庭成员人数与前列腺癌发病年龄 发病于受影响的家庭成员。高密度玉米的遗传连锁研究 前列腺癌家族导致了第一个本地化的 前列腺癌易感基因HPC1，定位于1q24-25。外加剂 测试表明，该基因可能与前列腺癌易感性有关。 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HPC1的存在提供了最有力的支持。在过去的六年里 几个月前，又提出了两个前列腺癌易感基因： 位于1q42.2-43的HPC2和位于Xq29-28的HPCX；独立验证这些基因座 目前还没有报道。 进一步支持HPC1对显著的 遗传性前列腺癌病例的比例和确定其他因素的作用 建议的易感基因座，包括HPC2和HPCX及其相关的 临床证候方面，提出了以下具体目标：1)检视 与HPC1和HPC1相关的前列腺癌家族的特征 其他HPC基因座用于确定该病独特的组织病理学和临床特征 这些家庭；2.)继续定义HPC1在遗传性疾病中的作用 前列腺癌；和3.评估其他潜在的高性能混凝土的贡献 遗传性前列腺癌的基因，包括1q42.2-43的HPC2和1q42.2-43的HPCX XQ27-28。这些研究将有助于提高我们对 前列腺癌易感基因及其相关临床症状。

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.