A Systematic Review of Replication Studies of Prostate Cancer Susceptibility Genetic Variants in High-Risk Men Originally Identified from Genome-Wide Association Studies

作者：Ishak Miriam B; Giri Veda N^*

来源：Cancer Epidemiology Biomarkers & Prevention, 2011, 20(8): 1599-1610.

DOI：10.1158/1055-9965.EPI-11-0312

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. Cancer Epidemiol Biomarkers Prev; 20(8); 1599-610.

• 出版日期2011-8