Prostate Cancer in a Black Population

黑人前列腺癌

• 批准号: 7409589
• 负责人: MCRISTINA LESKE
• 金额: $ 82.6万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-20 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409589
• 关键词: Admixture; Affect; African; African American; Alleles; Antigen Receptors; Barbados; Body Size; Cancer Etiology; Cancer Family; Candidate Disease Gene; Characteristics; Code; Conflict (Psychology); Data; Detection; Development; Diabetes Mellitus; Energy Intake; Evaluation; Family history of; Fatty acid glycerol esters; Future; Gene Structure; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glycosylated hemoglobin A; Goals; Gonadal Steroid Hormones; Growth Factor; Haplotypes; Height; High Prevalence; Hip region structure; Histologic; Hormones; Hyperinsulinism; Individual; Insulin; Invasive; Investigation; Joints; Life Style; Link; Malignant neoplasm of prostate; Measures; Mediating; Metabolic; Metabolism; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Other Genetics; Pathway interactions; Pattern; Persons; Population; Population Attributable Risks; Predisposition; Preventive Intervention; Public Health; Recording of previous events; Regulation; Research; Research Personnel; Resources; Risk; Risk Estimate; Risk Factors; Role; Sampling; Single Nucleotide Polymorphism Map; Staging; Testing; Time; Validation; Variant; Weight; West Indies; anticancer research; base; cancer risk; chemokine receptor; genetic analysis; genetic variant; indexing; interest; men; novel; programs; steroid hormone; steroid metabolism

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.

描述（由申请人提供）：前列腺癌（PC）不成比例地影响非洲裔美国人（AA）。这项研究提出，在为此类研究提供特殊机会的环境中，确定导致非洲裔人患PC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性事件病例和960例来自西印度群岛巴巴多斯的基于人群的对照男性，约94%为非洲-巴巴多斯人（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，并具有相似的PC模式。这些相似性表明遗传易感性在AA/AB中的作用，这可能是由于祖先的遗传变异。由于混合物较少，AB中这些变体的检测将得到增强;结果将在AA样本中重现。我们假设一个多基因模型的易感性，涉及胰岛素相关和类固醇激素途径，这也可能是介导的环境影响，中枢性肥胖模式将显着影响风险。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与其他指数不同）、体重史和其他因素的关系来实现。目的2：采用分阶段基因分型方法，评估PC与假设通路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对照者中参与胰岛素/IGF轴和类固醇代谢和调节途径的候选基因中的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，并随后确定与PC相关的风险估计在个别SNP和单倍型等位基因。第2阶段：我们将在800例AA PC病例和800例对照组中验证所有SNP/单倍型的前1%和SNP前5%中的所有编码SNP。该研究与AA具有高度的公共卫生相关性。它将通过识别新的遗传和其他风险因素来阐明AA中PC风险的原因。该研究将使用新的多基因和多阶段方法，涉及AA的数据，并专注于相关的PC途径。它还将确定与肥胖有关的因素的作用，其结果有可能用于预防干预。研究数据将允许在非洲散居地之间比较PC风险，并成为推进AA中PC研究的资源。