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

Published

Journal Article

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 HapMap 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.

Full Text

Duke Authors

Cited Authors

  • Goode, EL; Fridley, BL; Vierkant, RA; Cunningham, JM; Phelan, CM; Anderson, S; Rider, DN; White, KL; Pankratz, VS; Song, H; Hogdall, E; Kjaer, SK; Whittemore, AS; DiCioccio, R; Ramus, SJ; Gayther, SA; Schildkraut, JM; Pharaoh, PPD; Sellers, TA

Published Date

  • March 3, 2009

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 935 - 944

PubMed ID

  • 19258477

Pubmed Central ID

  • 19258477

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

International Standard Serial Number (ISSN)

  • 1055-9965

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-08-0860

Language

  • eng