Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

Research output: Contribution to journalJournal articleResearchpeer-review

  • Honglin Song
  • Susan J Ramus
  • Kjær, Susanne Krüger
  • Richard A DiCioccio
  • Georgia Chenevix-Trench
  • Celeste Leigh Pearce
  • Estrid Hogdall
  • Alice S Whittemore
  • Valerie McGuire
  • Claus Hogdall
  • Jan Blaakaer
  • Anna H Wu
  • David J Van Den Berg
  • Daniel O Stram
  • Usha Menon
  • Aleksandra Gentry-Maharaj
  • Ian J Jacobs
  • Penny M Webb
  • Jonathan Beesley
  • Xiaoqing Chen
  • Australian Cancer (Ovarian) Study
  • Australian Ovarian Cancer Study Group
  • Mary Anne Rossing
  • Jennifer A Doherty
  • Jenny Chang-Claude
  • Shan Wang-Gohrke
  • Marc T Goodman
  • Galina Lurie
  • Pamela J Thompson
  • Michael E Carney
  • Roberta B Ness
  • Kirsten Moysich
  • Ellen L Goode
  • Robert A Vierkant
  • Julie M Cunningham
  • Stephanie Anderson
  • Joellen M Schildkraut
  • Andrew Berchuck
  • Edwin S Iversen
  • Patricia G Moorman
  • Montserrat Garcia-Closas
  • Stephen Chanock
  • Jolanta Lissowska
  • Louise Brinton
  • Hoda Anton-Culver
  • Argyrios Ziogas
  • Wendy R Brewster
  • Bruce A J Ponder
  • Douglas F Easton
  • Simon A Gayther
  • Paul D P Pharoah
  • Ovarian Cancer Association Consortium (OCAC)
Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.
Original languageEnglish
JournalHuman Molecular Genetics
Volume18
Issue number12
Pages (from-to)2297-304
Number of pages7
ISSN0964-6906
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Breast Neoplasms; Case-Control Studies; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Glycoproteins; Humans; Neuropeptides; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Risk Factors

ID: 19977219