Genetics of Prostate Cancer in Africa

 描述(申请人提供)：前列腺癌(CAP)是全世界非洲裔男性最常见的癌症。非洲裔美国人(AA)患有世界上最高的CAP，2006-2010年期间的年均发病率为每10万人中有229人(SEER)。国际癌症研究机构(IARC)的GLOBOCAN项目估计，就非洲和加勒比地区男性的发病率和死亡率而言，CAP也是最主要的癌症。AA男性的攻击性帽子死亡率和帽子特定死亡率是美国所有种族中最高的。IARC还预测，撒哈拉以南非洲(SSA)的死亡上限将几乎翻一番，从2010年的55,522人增加到2030年的105,758人(即死亡人数是美国的两倍多)。尽管与其他种族或民族的男性相比，世界各地的非洲裔男性患有CAP的比例更高，但我们对造成这些差异的原因的理解仍然不完整。到目前为止，在CAP病因学中几乎没有发现暴露、生活方式或环境的影响。相比之下，CAP是最容易遗传的常见癌症之一，已经确定了90多个易感基因。然而，这些基因座中的许多都没有在再生障碍性贫血中复制，部分原因是非洲裔样本大小有限，对非洲等位基因的捕获不完整，以及对非洲基因组结构的了解有限。为了更好地了解非洲裔男性CAP的病因，我们发起了一个大型、多中心的联盟，名为“非洲裔男性和前列腺癌”(MADCAP)。利用该联盟的资源，我们建议在SSA中开展一项关于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：发现新的CAP基因座并验证非洲男性已知的CAP基因座，以提供有关CAP遗传病因学的新信息。具体目标2.人口基因组学：评估人口分化和非洲人和非洲裔美国人最近的进化史如何影响非裔美国人CAP发生率高的根本原因。这项建议将确定影响非洲人群中CAP风险的非洲等位基因，并将提供有关非洲基因组的信息，这些信息将对CAP和其他疾病的广泛基因组发现研究有价值。

 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.