Prostate Cancer in a Black Population

描述(申请人提供)：前列腺癌(PC)对非裔美国人(AA)的影响不成比例。这项研究建议在为这类研究提供特殊机会的环境中，确定导致非洲人后裔患前列腺癌风险的新的遗传和肥胖相关因素。结果将基于960例经组织学证实的全国病例和来自巴巴多斯、西印度群岛的960名以人口为基础的控制组男子，其中94%是非洲裔巴巴迪亚人(AB)。研究结果对AA具有较高的适用性。AA和AB群体具有相同的祖先起源和相似的PC模式。这些相似之处表明遗传易感性在AA/AB中起作用，这可能是由于祖先的遗传变异所致。这些变异的检测将在AB中得到加强，因为混合程度较低；结果将在AA样本中重复。我们假设了一个涉及胰岛素相关和类固醇激素途径的多基因易感性模型，这也可能受到环境影响的调节；中心性肥胖模式将显著影响风险。目的1：评估体型对PC风险的贡献。这一目标将通过确定与人体测量指数(AA/AB与其他指标不同)、体重历史和其他因素的关系来实现。目的：采用分阶段基因分型方法，评估PC与假想途径中常见遗传变异的关系。第一阶段：我们将对900例AB PC患者和900例AB对照的胰岛素/胰岛素样生长因子轴和类固醇代谢及调节途径相关候选基因中的800个SNP(2kb SNP图谱)进行基因分型和分析。我们将确定这些基因的单倍型块结构，并随后确定单个SNPs和单倍型的等位基因与PC相关的风险估计。阶段2：我们将在800例AA PC病例和800名对照中验证前1%的所有SNP/单倍型和前5%的SNP中的所有编码SNP。这项研究与再生障碍性贫血具有很高的公共卫生相关性。它将通过识别新的遗传和其他风险因素来澄清再生障碍性贫血中PC风险的原因。这项研究将使用新的多基因和多阶段方法，涉及再生障碍性贫血的数据，并专注于相关的PC途径。它还将确定肥胖相关因素的作用，其结果有可能成为预防性干预措施。研究数据将允许比较散居海外的非洲人的个人电脑风险，并成为推动再生障碍性疾病研究的资源。

DESCRIPTION (provided by applicant): Prostate cancer (PC) disproportionately affects African-Americans (AA). This study proposes to identify new genetic and obesity-related factors contributing to PC risk in persons of African descent, in a setting that offers special opportunities for such research. Results would be based on 960 histologically-confirmed nationwide incident cases and 960 population-based control men from Barbados, West Indies, -94% being African-Barbadians (AB). Study results have high applicability to AA. The AA and AB populations share the same ancestral origin and have similar PC patterns. These similarities suggest a role for inherited susceptibility in AA/AB, which could be due to ancestral genetic variants. Detection of these variants would be enhanced in AB because of lower admixture; results would be replicated in AA samples. We hypothesize a multigenic model of susceptibility involving insulin-related and steroid hormone pathways, which also may be mediated by environmental influences; central adiposity patterns would notably affect risk. AIM 1: To evaluate the contribution of body size to PC risk. This aim would be achieved by ascertaining relationships with anthropometric indices (which differ in AA/AB vs. others), weight history and other factors. AIM 2: To evaluate the relationship of PC to common genetic variants in hypothesized pathways, using a staged genotyping approach. Stage 1: we will genotype and analyze 800 SNPs (2kb SNP map) within select candidate genes involved in the insulin/IGF axis and steroid metabolism and regulation pathways among 900 AB PC cases and 900 AB controls. We will determine the haplotype block structure of these genes and subsequently determine risk estimates associated with PC for alleles at individual SNPs and haplotypes. Stage 2: we will validate the top 1% of all SNPs/haplotypes and all coding SNPs among the top 5% of SNPs in a set of 800 AA PC cases and 800 controls. The study has high public health relevance to AA. It would clarify reasons for PC risk in AA, by identifying new genetic and other risk factors. The study will use novel multigenic and multistage approaches, involving data on AA, and focus on relevant PC pathways. It will also determine the role of obesity-related factors, with results having potential for preventive interventions. Study data will allow comparisons of PC risk across the African diaspora, as well as being a resource to advance PC research in AA.