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

ABSTRACT: 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.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.We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined.These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies.These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.

SUBMITTER: White KL 

PROVIDER: S-EPMC3650102 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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

White Kristin L KL   Vierkant Robert A RA   Fogarty Zachary C ZC   Charbonneau Bridget B   Block Matthew S MS   Pharoah Paul D P PD   Chenevix-Trench Georgia G   Rossing Mary Anne MA   Cramer Daniel W DW   Pearce Celeste Leigh CL   Schildkraut Joellen M JM   Menon Usha U   Kjaer Susanne Kruger SK   Levine Douglas A DA   Gronwald Jacek J   Culver Hoda Anton HA   Whittemore Alice S AS   Karlan Beth Y BY   Lambrechts Diether D   Wentzensen Nicolas N   Kupryjanczyk Jolanta J   Chang-Claude Jenny J   Bandera Elisa V EV   Hogdall Estrid E   Heitz Florian F   Kaye Stanley B SB   Fasching Peter A PA   Campbell Ian I   Goodman Marc T MT   Pejovic Tanja T   Bean Yukie Y   Lurie Galina G   Eccles Diana D   Hein Alexander A   Beckmann Matthias W MW   Ekici Arif B AB   Paul James J   Brown Robert R   Flanagan James M JM   Harter Philipp P   du Bois Andreas A   Schwaab Ira I   Hogdall Claus K CK   Lundvall Lene L   Olson Sara H SH   Orlow Irene I   Paddock Lisa E LE   Rudolph Anja A   Eilber Ursula U   Dansonka-Mieszkowska Agnieszka A   Rzepecka Iwona K IK   Ziolkowska-Seta Izabela I   Brinton Louise L   Yang Hannah H   Garcia-Closas Montserrat M   Despierre Evelyn E   Lambrechts Sandrina S   Vergote Ignace I   Walsh Christine C   Lester Jenny J   Sieh Weiva W   McGuire Valerie V   Rothstein Joseph H JH   Ziogas Argyrios A   Lubinski Jan J   Cybulski Cezary C   Menkiszak Janusz J   Jensen Allan A   Gayther Simon A SA   Ramus Susan J SJ   Gentry-Maharaj Aleksandra A   Berchuck Andrew A   Wu Anna H AH   Pike Malcolm C MC   Van Denberg David D   Terry Kathryn L KL   Vitonis Allison F AF   Doherty Jennifer A JA   Johnatty Sharon E SE   Defazio Anna A   Song Honglin H   Tyrer Jonathan J   Sellers Thomas A TA   Phelan Catherine M CM   Kalli Kimberly R KR   Cunningham Julie M JM   Fridley Brooke L BL   Goode Ellen L EL  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130319 5

<h4>Background</h4>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.<h4>Methods</h4>Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genot  ...[more]