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


Authors: White, K. L.; Vierkant, R. A.; Fogarty, Z. C.; Charbonneau, B.; Block, M. S.; Pharoah, P. D. P.; Chenevix-Trench, G.; Rossing, M. A.; Cramer, D. W.; Pearce, C. L.; Schildkraut, J. M.; Menon, U.; Kjaer, S. K.; Levine, D. A.; Gronwald, J.; Culver, H. A.; Whittemore, A. S.; Karlan, B. Y.; Lambrechts, D.; Wentzensen, N.; Kupryjanczyk, J.; Chang-Claude, J.; Bandera, E. V.; Hogdall, E.; Heitz, F.; Kaye, S. B.; Fasching, P. A.; Campbell, I.; Goodman, M. T.; Pejovic, T.; Bean, Y.; Lurie, G.; Eccles, D.; Hein, A.; Beckmann, M. W.; Ekici, A. B.; Paul, J.; Brown, R.; Flanagan, J. M.; Harter, P.; du Bois, A.; Schwaab, I.; Hogdall, C. K.; Lundvall, L.; Olson, S. H.; Orlow, I.; Paddock, L. E.; Rudolph, A.; Eilber, U.; Dansonka-Mieszkowska, A.; Rzepecka, I. K.; 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, J. H.; Ziogas, A.; Lubinski, J.; Cybulski, C.; Menkiszak, J.; Jensen, A.; Gayther, S. A.; Ramus, S. J.; Gentry-Maharaj, A.; Berchuck, A.; Wu, A. H.; Pike, M. C.; Van DenBerg, D.; Terry, K. L.; Vitonis, A. F.; Doherty, J. A.; Johnatty, S. E.; Defazio, A.; Song, H.; Tyrer, J.; Sellers, T. A.; Phelan, C. M.; Kalli, K. R.; Cunningham, J. M.; Fridley, B. L.; Goode, E. L.
Article Title: 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,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. © 2013 American Association for Cancer Research.
Keywords: adult; cancer survival; controlled study; aged; survival analysis; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; disease course; cancer recurrence; mitosis; ovarian neoplasms; genetic predisposition to disease; ovary cancer; proportional hazards models; inflammation; genotype; angiogenesis; excision repair cross complementing protein 1; cancer mortality; polymorphism, genetic; interleukin 18; multidrug resistance protein 1; genetic association studies; xeroderma pigmentosum group d protein; cytochrome p450 2c8
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 22
Issue: 5
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2013-05-01
Start Page: 987
End Page: 992
Language: English
DOI: 10.1158/1055-9965.epi-13-0028
PROVIDER: scopus
PMCID: PMC3650102
PUBMED: 23513043
DOI/URL:
Notes: --- - "Export Date: 1 July 2013" - "CODEN: CEBPE" - "Source: Scopus"
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  1. Malcolm Pike
    190 Pike
  2. Sara H Olson
    234 Olson
  3. Douglas A Levine
    380 Levine
  4. Irene Orlow
    247 Orlow