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题目:: Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk.
作者:: Goode(Ellen L),Fridley(Brooke L),Vierkant(Robert A),Cunningham(Julie M),Phelan(Catherine M),Anderson(Stephanie),Rider(David N),White(Kristin L),Pankratz(V Shane),Song(Honglin),Hogdall(Estrid),Kjaer(Susanne K),Whittemore(Alice S),DiCioccio(Richard),Ramus(Susan J),Gayther(Simon A),Schildkraut(Joellen M),Pharaoh(Paul P D),Sellers(Thomas A)
状态:: 发布时间2009-03-10 , 更新时间 2016-11-22
期刊:: Cancer Epidemiol Biomarkers Prev
摘要:: 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.
语言:: eng
DOI:

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