Citations 2
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]
Polymorphism in theIL18Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women
Palmieri, Rachel T., Wilson, Melanie A., Iversen, Edwin S., Clyde, Merlise A. , Calingaert, Brian , Moorman, Patricia G. , Poole, Charles, Anderson, S. Keith , Beesley, Jonathan, Høgdall, Estrid , Carney, Michael E., Chen, Xiaoqing , Chenevix‐Trench, Georgia , Chang‐Claude, Jenny , Cunningham, Julie M. , DiCioccio, Richard A., Easton, Douglas F. , Edlund, Christopher K., Gayther, Simon A. , Goode, Ellen L. , Goodman, Marc T. , Kjær, Susanne K. , Høgdall, Claus , Hopkins, Michael P., Jenison, Eric L., Blaakær, Jan , Lurie, Galina, McGuire, Valerie, Menon, Usha , Moysich, Kirsten B. , Ness, Roberta B., Pearce, Celeste Leigh , Pike, Malcolm C. , Ramus, Susan J. , Rossing, Mary Anne, Song, Honglin , Terada, Keith Y. , VanDenBerg, David, Vierkant, Robert A. , Wang‐Gohrke, Shan , Webb, Penelope M. , Whittemore, Alice S. , Wu, Anna H. , Schildkraut, Joellen M. , Bowtell, David D.L. , Weber, Rachel Palmieri , Anderson, Alisha R. , Anton‐Culver, Hoda , Brewster, Wendy R. , Doherty, Jennifer A. , Gentry‐Maharaj, Aleksandra , Pharoah, Paul D.P. , Ziogas, Argyrios , Berchuck, Andrew , Kjaer, Susanne K , Ramus, Susan J , Webb, Penelope M , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Bowtell, David D , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | December 8, 2008 | Volume: 17 | Issue: 12 | Pages: 3567-3572
AbstractOver 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a <25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567–72)