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Title: Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome.
Authors: White KL,  Vierkant RA,  Fogarty ZC,  Charbonneau B,  Block MS,  Pharoah PD,  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
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2013 May
Branches: HREB
PubMed ID: 23513043
PMC ID: PMC3650102
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.