Genetics of Prostate Cancer in Africa

非洲前列腺癌的遗传学

• 批准号: 9756326
• 负责人: TIMOTHY R REBBECK
• 金额: $ 159.81万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-07 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756326
• 关键词: Address; Africa; Africa South of the Sahara; African; African American; Alleles; Architecture; Asians; Biological; Cancer Etiology; Caribbean region; Cessation of life; Detection; Diagnosis; Disease; Environmental Risk Factor; Ethnic Origin; Ethnic group; Etiology; European; Fostering; Gene Frequency; Genetic; Genetic Predisposition to Disease; Genome; Genomic Segment; Genomics; Heritability; Incidence; Infrastructure; International Agency for Research on Cancer; Knowledge; Life Style; Link; Malignant Neoplasms; Malignant neoplasm of prostate; Multicenter Studies; Pattern; Population; Prostate carcinoma; Public Health; Race; Recording of previous events; Reporting; Research; Resources; Risk; Sample Size; Sampling; Structure; Susceptibility Gene; Variant; anticancer research; experience; genome wide association study; improved; infrastructure development; men; mortality; novel; programs; public health relevance

 DESCRIPTION (provided by applicant): Prostate cancer (CaP) is the most common cancer in men of African descent worldwide. African Americans (AA) suffer from the highest rates of CaP in the world, with an average annual incidence rate of 229 per 100,000 in the period 2006-2010 (SEER). The International Agency for Research on Cancer (IARC) GLOBOCAN program estimates that CaP is also the leading cancer in terms of incidence and mortality in men from Africa and the Caribbean. AA men experience the highest rate of aggressive CaP and CaP-specific mortality of any ethnic group in the US. IARC also predicts that CaP deaths in sub-Saharan Africa (SSA) will almost double from 55,522 in 2010 to 105,758 by 2030 (i.e., more than twice as many deaths as in the US). While men of African descent around the world suffer disproportionately from CaP compared to men of other races or ethnicities, our understanding of the reasons for these disparities remains incomplete. To date, few exposure, lifestyle, or environmental influences have been identified in CaP etiology. In contrast, CaP is among the most heritable of common cancers, and over 90 susceptibility loci have been identified. However, many of these loci have not been replicated in AA, in part because of limited African descent sample sizes, incomplete capture of African alleles, and a limited understanding of African genomic architecture. To better understand the etiology of CaP in African descent men, we have initiated a large, multicenter consortium known as "Men of African Descent and Carcinoma of the Prostate" (MADCaP). Using resources of this consortium, we propose to undertake a multicenter study of CaP in SSA addressing the following Aims: Specific Aim 1: Genetic Susceptibility: Discover novel CaP loci and validate known CaP loci in African men to provide new information about the genetic etiology of CaP. Specific Aim 2. Population Genomics: Evaluate how population differentiation and the recent evolutionary history of African and African American populations inform the underlying reasons for the high rates of CaP in African Americans. This proposal will identify African alleles influence CaP risk in African populations, and will provide information about the African genome that will be of value to a wide range of genome discovery studies in CaP and other diseases.

 描述（由申请人提供）：前列腺癌 (CaP) 是全球非洲裔男性中最常见的癌症，非洲裔美国人 (AA) 的前列腺癌发病率是世界上最高的，平均年发病率为每 100,000 人 229 例。 2006 年至 2010 年期间 (SEER)，国际癌症研究机构 (IARC) GLOBOCAN 计划估计，就发病率和发病率而言，CaP 也是领先的癌症。非洲和加勒比地区男性的侵袭性 CaP 和特定 CaP 死亡率是美国所有族群中最高的。 2010 年，到 2030 年，这一数字将增至 105,758 人（即死亡人数是美国的两倍多），而世界各地的非洲裔男性则不成比例地遭受此类疾病的折磨。与其他种族或民族的男性相比，我们对这些差异的原因的理解仍然不完整，迄今为止，在 CaP 病因学中很少发现暴露、生活方式或环境影响，相反，CaP 是最常见的遗传因素之一。然而，其中许多基因座尚未在 AA 中复制，部分原因是非洲人后裔样本量有限、对非洲等位基因的捕获不完整以及对非洲人的了解有限。为了更好地了解非洲裔男性 CaP 的病因，我们发起了一个名为“非洲裔男性与前列腺癌”(MADCaP) 的大型多中心联盟，我们建议利用该联盟的资源开展研究。一项针对 SSA 中 CaP 的多中心研究，旨在实现以下目标： 具体目标 1：遗传易感性：发现非洲男性中新的 CaP 位点并验证已知的 CaP 位点，以提供有关遗传的新信息具体目标 2. 群体基因组学：评估非洲裔和非裔美国人群体的群体分化和近期进化史如何揭示非裔美国人 CaP 高发病率的根本原因。非洲人群，并将提供有关非洲基因组的信息，这对于 CaP 和其他疾病的广泛基因组发现研究有价值。