Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

Kristin L. White, Robert A. Vierkant, Zachary C. Fogarty, Bridget Charbonneau, Matthew S. Block, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne Kruger Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas WentzensenJolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie Bean, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas Du Bois, Ira Schwaab, Claus K. Hogdall, Lene Lundvall, Sara H. Olson, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Ursula Eilber, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Izabela Ziolkowska-Seta, Louise Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van DenBerg, Kathryn L. Terry, Allison F. Vitonis, Jennifer A. Doherty, Sharon E. Johnatty, Anna DeFazio, Honglin Song, Jonathan Tyrer, Thomas A. Sellers, Catherine M. Phelan, Kimberly R. Kalli, Julie M. Cunningham, Brooke L. Fridley, Ellen L. Goode

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome,weevaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-92.

Original languageEnglish (US)
Pages (from-to)987-992
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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