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

Abstract

BACKGROUND:

Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated 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.

• Authors: Kristin L White, Robert A Vierkant, Zachary C Fogarty, Bridget Charbonneau, Matthew S Block, Paul D P Pharoah, Georgia Chenevix-Trench, for AOCS/ACS group;, 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 Wentzensen, Jolanta 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 Lubinski, 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
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 22 Issue 5 Pg. 987-92 (May 2013) ISSN: 1538-7755 [Electronic] United States
• PMID: 23513043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Topics

• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Ovarian Neoplasms (genetics, mortality)
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Prognosis
• Proportional Hazards Models
• Survival Analysis