Polymorphism in the IL18 gene and epithelial ovarian cancer in non-hispanic white women

Rachel T. Palmieri, Melanie A. Wilson, Edwin S. Iversen, Merlise A. Clyde, Brian Calingaert, Patricia G. Moorman, Charles Poole, A. Rebecca Anderson, Stephanie Anderson, Hoda Anton-Culver, Jonathan Beesley, Estrid Hogdall, Wendy Brewster, Michael E. Carney, Xiaoqing Chen, Georgia Chenevix-Trench, Jenny Chang-Claude, Julie M. Cunningham, Richard A. DiCioccio, Jennifer A. DohertyDouglas F. Easton, Christopher K. Edlund, Simon A. Gayther, Aleksandra Gentry-Maharaj, Ellen L. Goode, Marc T. Goodman, Susanne Kruger Kjaer, Claus K. Hogdall, Michael P. Hopkins, Eric L. Jenison, Jan Blaakaer, Galina Lurie, Valerie McGuire, Usha Menon, Kirsten B. Moysich, Roberta B. Ness, Celeste Leigh Pearce, Paul D.P. Pharoah, Malcolm C. Pike, Susan J. Ramus, Mary Anne Rossing, Honglin Song, Keith Y. Terada, David VanDenBerg, Robert A. Vierkant, Shan Wang-Gohrke, Penelope M. Webb, Alice S. Whittemore, Anna H. Wu, Argyrios Ziogas, Andrew Berchuck, Joellen M. Schildkraut

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Over 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.

Original languageEnglish (US)
Pages (from-to)3567-3572
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Issue number12
StatePublished - Dec 2008

ASJC Scopus subject areas

  • General Medicine


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