Genetics of Prostate Cancer in Africa

 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）患有世界上最高的CaP率，2006-2010年期间的平均年发病率为每10万人229例（SEER）。国际癌症研究机构（IARC）GLOBOCAN计划估计，CaP也是非洲和加勒比地区男性发病率和死亡率最高的癌症。在美国，AA男性的侵袭性CaP和CaP特异性死亡率是所有种族中最高的。IARC还预测，到2030年，撒哈拉以南非洲（SSA）的CaP死亡人数将从2010年的55，522人增加到105，758人（即，死亡人数是美国的两倍多）。虽然与其他种族或族裔的男性相比，世界各地的非洲裔男性不成比例地遭受CaP，但我们对这些差异的原因的理解仍然不完整。到目前为止，很少有暴露，生活方式，或环境的影响已被确定在CaP病因。相比之下，CaP是最易遗传的常见癌症之一，并且已经鉴定了超过90个易感基因座。然而，这些基因座中的许多基因座在AA中没有被复制，部分原因是非洲血统样本量有限，非洲等位基因捕获不完整，以及对非洲基因组结构的理解有限。 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联盟，称为“非洲裔男性和前列腺癌”（MADCaP）。利用该联盟的资源，我们建议进行一项多中心研究，在SSA解决以下目标：具体目标1：遗传易感性：发现新的CaP基因座和验证已知的CaP基因座在非洲男性提供新的信息，遗传病因的CaP。 具体目标2。群体基因组学：评估非洲和非洲裔美国人的人口分化和最近的进化史如何告知非洲裔美国人CaP高发病率的根本原因。 该提案将确定非洲等位基因影响非洲人群中的CaP风险，并将提供有关非洲基因组的信息，这些信息对CaP和其他疾病的广泛基因组发现研究具有价值。

 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.