Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium

Carcinogenesis. 2012 Feb;33(2):356-60. doi: 10.1093/carcin/bgr279. Epub 2011 Nov 23.

Abstract

A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10(-8) for rs12653946 at 5p15, 4.43 × 10(-5) for rs339331 at 6q22 and 8.42 × 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 2.58 × 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Asian People / genetics*
  • Case-Control Studies
  • DNA-Binding Proteins / genetics
  • Gene Frequency
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Male
  • Neoplasm Grading
  • Odds Ratio
  • Prostatic Neoplasms / genetics*
  • RNA, Messenger / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Regulatory Factor X Transcription Factors
  • Risk
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • GPRC6A protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Regulatory Factor X Transcription Factors
  • Rfx6 protein, human
  • Transcription Factors