A Genome-Wide Association Study Identifies a New Ovarian Cancer Susceptibility Locus on 9p22.2

Nat Genet. 2009 Sep;41(9):996-1000. doi: 10.1038/ng.424. Epub 2009 Aug 2.

Abstract

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

Publication types

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

MeSH terms

  • Alleles
  • Australia
  • Base Sequence
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9*
  • Confidence Intervals
  • Europe
  • European Continental Ancestry Group / genetics
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Molecular Sequence Data
  • Odds Ratio
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • United States

Grant support