Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1599-610. doi: 10.1158/1055-9965.EPI-11-0312. Epub 2011 Jun 29.
Several prostate cancer genome-wide association studies (GWAS) have identified risk-associated genetic variants primarily in populations of European descent. Less is known about the association of these variants in high-risk populations, including men of African descent and men with a family history of prostate cancer. This article provides a detailed review of published studies of prostate cancer-associated genetic variants originally identified in GWAS and replicated in high-risk populations.
Articles replicating GWAS findings (National Human Genome Research Institute GWAS database) were identified by searching PubMed and relevant data were extracted.
Eleven replication studies were eligible for inclusion in this review. Of more than 30 single-nucleotide polymorphisms (SNP) identified in prostate cancer GWAS, 19 SNPs (63%) were replicated in men of African descent and 10 SNPs (33%) were replicated in men with familial and/or hereditary prostate cancer (FPC/HPC). The majority of SNPs were located at the 8q24 region with modest effect sizes (OR 1.11-2.63 in African American men and OR 1.3-2.51 in men with FPC). All replicated SNPs at 8q24 among men of African descent were within or near regions 2 and 3.
This systematic review revealed several GWAS markers with replicated associations with prostate cancer in men of African descent and men with FPC/HPC. The 8q24 region continues to be the most implicated in prostate cancer risk. These replication data support ongoing study of clinical utility and potential function of these prostate cancer-associated variants in high-risk men.
The replicated SNPs presented in this review hold promise for personalizing risk assessment for prostate cancer for high-risk men upon further study.
几项前列腺癌全基因组关联研究（GWAS）主要在欧洲血统人群中鉴定出与风险相关的遗传变异。在包括非洲裔男性和有前列腺癌家族史的男性在内的高危人群中，这些变异的相关性知之甚少。本文详细回顾了最初在 GWAS 中发现并在高危人群中复制的与前列腺癌相关的遗传变异的已发表研究。
通过搜索 PubMed 并提取相关数据，确定了复制 GWAS 发现的文章（国家人类基因组研究所 GWAS 数据库）。
有 11 项符合纳入本综述标准的复制研究。在前列腺癌 GWAS 中鉴定出的 30 多个单核苷酸多态性（SNP）中，有 19 个 SNP（63%）在非洲裔男性中得到复制，有 10 个 SNP（33%）在有家族性和/或遗传性前列腺癌（FPC/HPC）的男性中得到复制。大多数 SNP 位于 8q24 区域，效应大小适中（在非洲裔美国男性中为 1.11-2.63，在有 FPC 的男性中为 1.3-2.51）。在非洲裔男性中，8q24 上所有复制的 SNP 均位于第 2 和第 3 区或附近。
本系统评价揭示了几项在非洲裔男性和有 FPC/HPC 的男性中与前列腺癌具有复制相关性的 GWAS 标记物。8q24 区域仍然是与前列腺癌风险最相关的区域。这些复制数据支持对这些与前列腺癌相关的变异在高危男性中的临床实用性和潜在功能进行进一步研究。
本综述中提出的复制 SNP 有望在进一步研究后为高危男性的前列腺癌风险评估提供个性化服务。
