HEREDITARY PROSTATE CANCER IN AFRICAN AMERICAN FAMILIES

前列腺癌的家族史已被证明是最重要的因素之一 前列腺癌的危险因素。使用隔离 分析，研究人员已经证明，早发性前列腺癌， 在一些家庭中，可能是由常染色体显性遗传的一个 罕见易感等位基因第一个假定的基因位点 具有遗传性的前列腺癌易感性，称为HPCl 位于染色体1q24 - 25，最近通过分析一组 前列腺癌的高危家庭。分析一组独立的 我们实验室的家庭也发现了前列腺癌的证据 与染色体1q标记连锁。前列腺癌是一种 非洲裔美国人的重要健康问题，因为年龄调整后， 非裔美国人前列腺癌的发病率大约是 比美国白人男性高出50%。相对风险 与前列腺癌的家族史相关的是相似的， 非洲裔和高加索裔美国人强调 在两个种族群体中诱发生殖系突变。非裔美国人 然而，在对遗传性疾病的研究中， 易患前列腺癌此外，对六个非洲国家的分析表明， 我们实验室的美国家庭表明，HPCl可能特别 在这个人群中很重要。为了验证HPC I参与 非裔美国人家庭的前列腺癌易感性， 提出了以下具体目标：I.识别非裔美国人 有两个或两个以上在世家庭成员患有前列腺疾病的家庭 癌二.分离DNA并对所有在 特异性目的I使用跨越HPC I的一组多态性标记 候选区间三.使用参数和非参数多点 分析以评估前列腺癌与映射到前列腺癌的标记物的关联， 1q24 - 25。四.收集所有可用的前列腺癌肿瘤样本 杂合性缺失（洛）是一种特征性的 多个肿瘤抑制基因，位于1q24 - 25。如果将HPCl基因克隆到 在这一建议的时间框架内，提出了额外的实验， 表征潜在的HPCl突变并测试与其他HPCl突变的关联。 前列腺癌家系中潜在的前列腺癌易感基因 不是由于HPCl基因突变引起的癌症。

A family history of prostate cancer has been shown to be one of the most important determinants of prostate cancer risk. Using segregation analysis, investigators have demonstrated that early-onset prostate cancer in some families may be explained by autosomal dominant inheritance of a rare susceptibility allele. The first putative genetic locus associated with the inherited predisposition to prostate cancer, referred to as HPCl at chromosome 1q24-25, was recently identified through analysis of a set of high-risk prostate cancer families. Analysis of an independent set of families in our laboratory has also revealed evidence of prostate cancer linkage to chromosome 1q markers. Prostate cancer is an exceedingly important health problem for African American men, since the age-adjusted incidence of prostate cancer in African American men is approximately fifty percent greater than in Caucasian American men. The relative risk associated with a family history of prostate cancer is similar between African and Caucasian American men emphasizing the importance of predisposing germline mutations in both ethnic cohorts. African American families, however, have been under-represented in studies of the inherited predisposition to prostate cancer. Furthermore, analysis of six African American families in our laboratory suggests that HPCl may be particularly important in this population. To test the hypothesis that HPCl contributes to prostate cancer predisposition in African American families, the following Specific Aims are proposed: I. Identify African American families with two or more living family members affected with prostate cancer. II. Isolate DNA and genotype all individuals identified at Specific Aim I using a panel of polymorphic markers spanning the HPCl candidate interval. III. Use parametric and non-parametric multipoint analysis to assess for linkage of prostate cancer to markers that map to 1q24-25. IV. Collect all available tumor samples from prostate cancer patients for analysis of loss of heterozygosity (LOH), a characteristic of many tumor suppressor genes, at 1q24-25. If the HPCl gene is cloned within the time frame of this proposal, additional experiments are proposed to characterize potential HPCl mutations and to test for linkage to other potential prostate cancer susceptibility loci in families with prostate cancer that is not due to mutations in the HPCl gene.