Dataset Information

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

ABSTRACT: 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. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567-72).

SUBMITTER: Palmieri RT

PROVIDER: S-EPMC2664299 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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

Palmieri Rachel T RT Wilson Melanie A MA Iversen Edwin S ES Clyde Merlise A MA Calingaert Brian B Moorman Patricia G PG Poole Charles C Anderson A Rebecca AR Anderson Stephanie S Anton-Culver Hoda H Beesley Jonathan J Hogdall Estrid E Brewster Wendy W Carney Michael E ME Chen Xiaoqing X Chenevix-Trench Georgia G Chang-Claude Jenny J Cunningham Julie M JM Dicioccio Richard A RA Doherty Jennifer A JA Easton Douglas F DF Edlund Christopher K CK Gayther Simon A SA Gentry-Maharaj Aleksandra A Goode Ellen L EL Goodman Marc T MT Kjaer Susanne Kruger SK Hogdall Claus K CK Hopkins Michael P MP Jenison Eric L EL Blaakaer Jan J Lurie Galina G McGuire Valerie V Menon Usha U Moysich Kirsten B KB Ness Roberta B RB Pearce Celeste Leigh CL Pharoah Paul D P PD Pike Malcolm C MC Ramus Susan J SJ Rossing Mary Anne MA Song Honglin H Terada Keith Y KY Vandenberg David D Vierkant Robert A RA Wang-Gohrke Shan S Webb Penelope M PM Whittemore Alice S AS Wu Anna H AH Ziogas Argyrios A Berchuck Andrew A Schildkraut Joellen M JM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20081201 12

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. ...[more]

PMID: 19064572

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Project description:BackgroundPreterm birth (PTB) disproportionately affects African American compared with Caucasian women, although reasons for this disparity remain unclear. Some suggest that a differential effect of maternal age by race/ethnicity, especially at older maternal ages, may explain disparities.ObjectiveTo determine whether the relationship between maternal age and preterm birth varies by race/ethnicity among primiparae non-Hispanic blacks (NHB) and non-Hispanic whites (NHW).MethodsA cross-sectional study of 367 081 singleton liveborn first births to NHB and NHW women in California from 2008 to 2012 was conducted. Rate ratios (RR) were estimated for PTB and its subtypes-spontaneous and clinician-initiated-after adjusting for confounders through Poisson regression. Universal age/race reference groups (NHW, 25-29 years) and race-specific reference groups (NHW or NHB, 25-29 years) were used for comparisons.ResultsAmong all women, RR of PTB was highest at the extremes of age (<15 and ≥40 years). Among NHBs, the risk of PTB was higher than among NHWs at all maternal ages (adjusted RR of PTB 1.38-2.93 vs 0.98-2.38). However, using race-specific reference groups, the risk of PTB for NHB women (RR 0.91-1.88) vs NHW women (RR 0.98-2.39) was nearly identical at all maternal ages, with overlapping confidence intervals. Analyses did not demonstrate substantial divergence of risk with advancing maternal age. PTB, spontaneous PTB, and clinician-initiated PTB demonstrated similar risk patterns at younger but not older maternal ages, where risk of clinician-initiated PTB increased sharply for all women.ConclusionsPrimiparae NHBs demonstrated increased risk of PTB, spontaneous PTB, and clinician-initiated PTB compared with NHWs at all maternal ages. However, RRs using race-specific reference groups converged across maternal ages, indicating a similar independent effect of maternal age on PTB by race/ethnicity. A differential effect of maternal age does not appear to explain disparities in preterm birth by race/ethnicity.

Dataset Information

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

Publications

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

Similar Datasets

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