Candidate gene analysis using imputed genotypes: Cell cycle single-nucleotide polymorphisms and ovarian cancer risk

Ellen L. Goode, Brooke L. Fridley, Robert A. Vierkant, Julie M. Cunningham, Catherine M. Phelan, Stephanie Anderson, David N. Rider, Kristin L. White, V. Shane Pankratz, Honglin Song, Estrid Hogdall, Susanne K. Kjaer, Alice S. Whittemore, Richard DiCioccio, Susan J. Ramus, Simon A. Gayther, Joellen M. Schildkraut, Paul P.D. Pharaoh, Thomas A. Sellers

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from existing genotype data, we conducted a combined analysis of five independent studies of invasive epithelial ovarian cancer. Up to 2,120 cases and 3,382 controls were genotyped in the course of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B). Because of the semi-overlapping nature of the 123 assayed tagging SNPs, we performed multiple imputation based on fastPHASE using data from White non-Hispanic study participants and participants in the international Hap-Map Consortium and National Institute of Environmental Health Sciences SNPs Program. Logistic regression assuming a log-additive model was done on combined and imputed data. We observed strengthened signals in imputation-based analyses at several SNPs, particularly CDKN2A-CDKN2B rs3731239; CCND1 rs602652, rs3212879, rs649392, and rs3212891; CDK2 rs2069391, rs2069414, and rs17528736; and CCNE1 rs3218036. These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls.

Original languageEnglish (US)
Pages (from-to)935-944
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number3
StatePublished - Mar 2009

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Candidate gene analysis using imputed genotypes: Cell cycle single-nucleotide polymorphisms and ovarian cancer risk'. Together they form a unique fingerprint.

Cite this