Citations 22
Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer
Schildkraut, Joellen M. , Goode, Ellen L. , Clyde, Merlise A. , Iversen, Edwin S., Moorman, Patricia G. , Marks, Jeffrey R. , Lissowska, Jolanta , Brinton, Louise A. , Pepłońska, Beata , Cunningham, Julie M. , Vierkant, Robert A. , Rider, David N., Chenevix‐Trench, Georgia , Webb, Penelope M. , Beesley, Jonathan, Chen, Xiaoqing, Phelan, Catherine, Sutphen, Rebecca , Sellers, Thomas A. , Pearce, Leigh, Wu, Anna H. , Conti, David V. , Elund, Christopher K., Anderson, Rebecca L. , Goodman, Marc T. , Lurie, Galina, Carney, Michael E., Thompson, Pamela J., Gayther, Simon A. , Ramus, Susan J. , Jacobs, Ian , Kjær, Susanne K. , Høgdall, Estrid , Blaakær, Jan , Høgdall, Claus , Easton, Douglas F. , Song, Honglin , Whittemore, Alice S. , McGuire, Valerie , Quaye, Lydia, Terry, Kathryn L. , Hankinson, Susan E. , Tworoger, Shelley S. , García‐Closas, Montserrat , Cancer), Australian Cancer Study (Ovarian, Group, Australian Ovarian Cancer Study, Berchuck, Andrew , Chen, Xiaoqing, Berg, David Van Den , Pharoah, Paul D.P. , Anton‐Culver, Hoda , Ziogas, Argyrios , Cramer, Daniel W. , Calingaert, Brian , Chanock, Stephen Jacob , Sherman, Mark E. , Cancer), Australian Cancer Study (Ovarian, Group, Australian Ovarian Cancer Study, Kjaer, Susanne K , Ramus, Susan J , Tworoger, Shelley S , Webb, Penelope M , Vierkant, Robert A , Lissowska, Jolanta , García-Closas, Montserrat , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Conti, David V , Goodman, Marc T
Cancer Research | March 10, 2009 | Volume: 69 | Issue: 6 | Pages: 2349-2357
Abstract The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP) in the TP53 region. Significant findings from this discovery phase were followed up for replication in the other OCAC studies. Mixed effects logistic regression was used to generate posterior median per allele odds ratios (OR), 95% probability intervals (PI), and Bayes factors (BF) for genotype associations. Five SNPs showed significant associations with risk in one or more of the discovery investigations and were followed up by OCAC. Mixed effects analysis confirmed associations with serous invasive cancers for two correlated (r2 = 0.62) SNPs: rs2287498 (median per allele OR, 1.30; 95% PI, 1.07–1.57) and rs12951053 (median per allele OR, 1.19; 95% PI, 1.01–1.38). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated with common variants in the TP53 region. [Cancer Res 2009;69(6):2349–57]
Tagging Single Nucleotide Polymorphisms in Cell Cycle Control Genes and Susceptibility to Invasive Epithelial Ovarian Cancer
Gayther, Simon A. , Song, Honglin , Ramus, Susan J. , Kjær, Susanne K. , Whittemore, Alice S. , Quaye, Lydia, Shadforth, Danielle, Høgdall, Estrid , Høgdall, Claus , Blaeker, Jan, DiCioccio, Richard A., McGuire, Valerie , Webb, Penelope M. , Beesley, Jonathan, Whiteman, David C. , Group, The Australian Ovarian Cancer Study, Cancer), The Australian Cancer Study (Ovarian, Goodman, Marc T. , Lurie, Galina, Carney, Michael E., Ness, Roberta B., Edwards, Robert P., Moysich, Kirsten B., Goode, Ellen L. , Cunningham, Julie M. , Sellers, Thomas A. , Wu, Anna H. , Pike, Malcolm C. , Iversen, Edwin S., Marks, Jeffrey R. , García‐Closas, Montserrat , Brinton, Louise A. , Lissowska, Jolanta , Pepłońska, Beata , Easton, Douglas F. , Jacobs, Ian , Ponder, Bruce A.J., Schildkraut, Joellen M. , Pearce, Celeste Leigh, Chenevix‐Trench, Georgia , Pharoah, Paul D.P., Blaakær, Jan , Tyrer, Jonathan P. , Green, Adèle C. , Group, The Australian Ovarian Cancer Study, Cancer), The Australian Cancer Study (Ovarian, Modugno, Francesmary , Couch, Fergus J. , Berchuck, Andrew , Kjaer, Susanne K , Ramus, Susan J , Webb, Penelope M , Moysich, Kirsten , Lissowska, Jolanta , García-Closas, Montserrat , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Whiteman, David C , Goodman, Marc T
Cancer Research | April 4, 2007 | Volume: 67 | Issue: 7 | Pages: 3027-3035
Abstract 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. [Cancer Res 2007;67(7):3027–35]