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

Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1599-610. doi: 10.1158/1055-9965.EPI-11-0312. Epub 2011 Jun 29.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / genetics*