A systematic review of replication studies of prostate cancer susceptibility genetic variants in high-risk men originally identified from genome-wide association studies

Abstract

Background: 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. Methods: Articles replicating GWAS findings (National Human Genome Research Institute GWAS database) were identified by searching PubMed and relevant data were extracted. Results: 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. Conclusions: 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. Impact: The replicated SNPs presented in this review hold promise for personalizing risk assessment for prostate cancer for high-risk men upon further study. ©2011 AACR.