Genome-wide association study identifies new prostate cancer susceptibility loci

Hum Mol Genet. 2011 Oct 1;20(19):3867-75. doi: 10.1093/hmg/ddr295. Epub 2011 Jul 8.

Abstract

Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.

Publication types

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

MeSH terms

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