Consortium analysis of 7 candidate SNPs for ovarian cancer

Int J Cancer. 2008 Jul 15;123(2):380-388. doi: 10.1002/ijc.23448.

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach.

Publication types

  • Multicenter 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

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics
  • Apoptosis Regulatory Proteins
  • Aurora Kinase A
  • Aurora Kinases
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Carcinoma / genetics*
  • Case-Control Studies
  • Caspase 8 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genotype
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Odds Ratio
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Single Nucleotide*
  • Protein-Serine-Threonine Kinases / genetics
  • Retinoblastoma Protein / genetics
  • Transforming Growth Factor beta1 / genetics

Substances

  • Apoptosis Regulatory Proteins
  • BLID protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • Retinoblastoma Protein
  • Transforming Growth Factor beta1
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • CASP8 protein, human
  • Caspase 8