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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • White, KL; Vierkant, RA; Fogarty, ZC; Charbonneau, B; Block, MS; Pharoah, PDP; Chenevix-Trench, G; for AOCS/ACS group;, ; Rossing, MA; Cramer, DW; Pearce, CL; Schildkraut, JM; Menon, U; Kjaer, SK; Levine, DA; Gronwald, J; Culver, HA; Whittemore, AS; Karlan, BY; Lambrechts, D; Wentzensen, N; Kupryjanczyk, J; Chang-Claude, J; Bandera, EV; Hogdall, E; Heitz, F; Kaye, SB; Fasching, PA; Campbell, I; Goodman, MT; Pejovic, T; Bean, Y; Lurie, G; Eccles, D; Hein, A; Beckmann, MW; Ekici, AB; Paul, J; Brown, R; Flanagan, JM; Harter, P; du Bois, A; Schwaab, I; Hogdall, CK; Lundvall, L; Olson, SH; Orlow, I; Paddock, LE; Rudolph, A; Eilber, U; Dansonka-Mieszkowska, A; Rzepecka, IK; Ziolkowska-Seta, I; Brinton, L; Yang, H; Garcia-Closas, M; Despierre, E; Lambrechts, S; Vergote, I; Walsh, C; Lester, J; Sieh, W; McGuire, V; Rothstein, JH; Ziogas, A; Lubinski, J; Cybulski, C; Menkiszak, J; Jensen, A; Gayther, SA; Ramus, SJ; Gentry-Maharaj, A; Berchuck, A; Wu, AH; Pike, MC; Van Denberg, D; Terry, KL; Vitonis, AF; Doherty, JA; Johnatty, SE; Defazio, A; Song, H; Tyrer, J; Sellers, TA; Phelan, CM; Kalli, KR; Cunningham, JM; Fridley, BL; Goode, EL

Published Date

  • May 2013

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 987 - 992

PubMed ID

  • 23513043

Pubmed Central ID

  • 23513043

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-13-0028

Language

  • eng

Conference Location

  • United States