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

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.