TY - JOUR
T1 - Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk
AU - Goode, Ellen L
AU - Fridley, Brooke L
AU - Vierkant, Robert A
AU - Cunningham, Julie M
AU - Phelan, Catherine M
AU - Anderson, Stephanie
AU - Rider, David N
AU - White, Kristin L
AU - Pankratz, V Shane
AU - Song, Honglin
AU - Hogdall, Estrid
AU - Kjaer, Susanne K
AU - Whittemore, Alice S
AU - DiCioccio, Richard
AU - Ramus, Susan J
AU - Gayther, Simon A
AU - Schildkraut, Joellen M
AU - Pharaoh, Paul P D
AU - Sellers, Thomas A
N1 - Keywords: Adult; Aged; Alleles; Case-Control Studies; Cell Cycle; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Female; Genotype; Humans; Logistic Models; Markov Chains; Middle Aged; Minnesota; Neoplasm Invasiveness; North Carolina; Oncogene Proteins; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Registries; Risk
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1158/1055-9965.EPI-08-0860
DO - 10.1158/1055-9965.EPI-08-0860
M3 - Journal article
C2 - 19258477
SN - 1055-9965
VL - 18
SP - 935
EP - 944
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
IS - 3
ER -
