Genome-wide association study identifies multiple loci associated with bladder cancer risk

Hum Mol Genet. 2014 Mar 1;23(5):1387-98. doi: 10.1093/hmg/ddt519. Epub 2013 Oct 24.

Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Case-Control Studies
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Meta-Analysis as Topic
  • Polymorphism, Single Nucleotide
  • Risk
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology