Common Variants at 19p13 Are Associated With Susceptibility to Ovarian Cancer

Nat Genet. 2010 Oct;42(10):880-4. doi: 10.1038/ng.666. Epub 2010 Sep 19.

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

Publication types

  • Comparative Study
  • 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

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 19 / genetics*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Ovary / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • BABAM1 protein, human
  • Biomarkers, Tumor

Grant support