PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: Results from the Breast and Prostate Cancer Cohort Consortium (BPC3)

Laure Dossus, Rudolf Kaaks, Federico Canzian, Demetrius Albanes, Sonja I. Berndt, Heiner Boeing, Julie Buring, Stephen J. Chanock, Francoise Clavel-Chapelon, Heather Spencer Feigelson, John M. Gaziano, Edward Giovannucci, Carlos Gonzalez, Christopher A. Haiman, Göran Hallmans, Susan E. Hankinson, Richard B. Hayes, Brian E. Henderson, Robert N. Hoover, David J. HunterKay Tee Khaw, Laurence N. Kolonel, Peter Kraft, Jing Ma, Loic Le Marchand, Eiliv Lund, Petra H.M. Peeters, Meir Stampfer, Dan O. Stram, Gilles Thomas, Michael J. Thun, Anne Tjonneland, Dimitrios Trichopoulos, Rosario Tumino, Elio Riboli, Jarmo Virtamo, Stephanie J. Weinstein, Meredith Yeager, Regina G. Ziegler, David G. Cox

Research output: Contribution to journalArticlepeer-review

Abstract

Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, Ptrend = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; Ptrend = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; Ptrend = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers.

Original languageEnglish (US)
Pages (from-to)455-461
Number of pages7
JournalCarcinogenesis
Volume31
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Cancer Research

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