TY - JOUR
T1 - Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer
AU - Gayther, Simon A.
AU - Song, Honglin
AU - Ramus, Susan J.
AU - Kjaer, Susan Krüger
AU - Whittemore, Alice S.
AU - Quaye, Lydia
AU - Tyrer, Jonathan
AU - Shadforth, Danielle
AU - Hogdall, Estrid
AU - Hogdall, Claus
AU - Blaeker, Jan
AU - DiCioccio, Richard
AU - McGuire, Valerie
AU - Webb, Penelope M.
AU - Beesley, Jonathan
AU - Green, Adele C.
AU - Whiteman, David C.
AU - Goodman, Marc T.
AU - Lurie, Galina
AU - Carney, Michael E.
AU - Modugno, Francesmary
AU - Ness, Roberta B.
AU - Edwards, Robert P.
AU - Moysich, Kirsten B.
AU - Goode, Ellen L.
AU - Couch, Fergus J.
AU - Cunningham, Julie M.
AU - Sellers, Thomas A.
AU - Wu, Anna H.
AU - Pike, Malcolm C.
AU - Iversen, Edwin S.
AU - Marks, Jeffrey R.
AU - Garcia-Closas, Montserrat
AU - Brinton, Louise
AU - Lissowska, Jolanta
AU - Peplonska, Beata
AU - Easton, Douglas F.
AU - Jacobs, Ian
AU - Ponder, Bruce A.J.
AU - Schildkraut, Joellen
AU - Pearce, C. Leigh
AU - Chenevix-Trench, Georgia
AU - Berchuck, Andrew
AU - Pharoah, Paul D.P.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - High-risk susceptibility genes explain <40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common variants in 13 genes involved in cell cycle control - CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D - and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotyped in three studies from the United Kingdom, United States, and Denmark (∼1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States (∼2,000 cases and ∼3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk [OR, 0.91 (0.85-0.98) for rs3731257; and OR, 0.93 (0.87-0.995) for rs2066827]. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies.
AB - High-risk susceptibility genes explain <40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common variants in 13 genes involved in cell cycle control - CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D - and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotyped in three studies from the United Kingdom, United States, and Denmark (∼1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States (∼2,000 cases and ∼3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk [OR, 0.91 (0.85-0.98) for rs3731257; and OR, 0.93 (0.87-0.995) for rs2066827]. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies.
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U2 - 10.1158/0008-5472.CAN-06-3261
DO - 10.1158/0008-5472.CAN-06-3261
M3 - Article
C2 - 17409409
AN - SCOPUS:34248160895
SN - 0008-5472
VL - 67
SP - 3027
EP - 3035
JO - Cancer research
JF - Cancer research
IS - 7
ER -