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British Journal of Cancer (2007) 97, 557-561.
doi:10.1038/sj.bjc.6603874 www.bjcancer.com Published online 3 July 2007
COX2 genetic variation, NSAIDs, and advanced prostate cancer risk
I Cheng1,2, X Liu3, S J Plummer4, L M Krumroy4, G Casey4 and J S Witte1,2
1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0794, USA
2Center of Human Genetics, University of California, San Francisco, CA 94143-0794, USA
3Department of Pediatrics, Northwestern University, Feinberg Mary Ann and J Milburn Smith Child Health Research Program, School of Medicine and Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL 60614, USA
4Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA
Correspondence to: Professor JS Witte, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0794, USA. E-mail: wittej@humgen.ucsf.edu
Received 2 February 2007; revised 7 June 2007; accepted 11 June 2007; published online 3 July 2007
Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate cancer. Nine single-nucleotide polymorphisms (SNPs) in COX2 were genotyped among 1012 men in our case-control study of advanced prostate cancer. Gene-environment interactions between COX2 polymorphisms and NSAID use were also evaluated. Information on NSAID use was obtained by questionnaire. Three SNPs demonstrated nominally statistically significant associations with prostate cancer risk, with the most compelling polymorphism (rs2745557) associated with a lower risk of disease (odds ratio (OR) GC vs GG=0.64; 95% confidence interval (CI): 0.49-0.84; P=0.002). We estimated through permutation analysis that a similarly strong result would occur by chance 2.7% of the time. Nonsteroidal anti-inflammatory drug use was associated with a lower risk of disease in comparison to no use (OR=0.67; 95% CI: 0.52-0.87). No significant statistical interaction between NSAID use and rs2745557 was observed (P=0.12). Our findings suggest that variation in COX2 is associated with prostate cancer risk.
Keywords: COX2; polymorphism; NSAIDs; prostate cancer
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| Print ISSN: 0007-0920 | Online ISSN: 1532-1827 | © 2007 Cancer Research UK | ||
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