No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARδ and PPARγ act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma

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Abstract
Regular continuous non-steroidal anti-inflammatory drug (NSAID) use has been associated with a reduction in risk of colorectal cancer. Our objective was to investigate whether or not a number of the polymorphic genes involved in the metabolism of NSAIDs, including cytochrome P450 s (CYPs), act as modifiers of this protective effect. As part of a multi-centre case-control study, 478 colorectal cancer patients and 733 controls (433 matched case-control pairs) answered questions on NSAID use. These individuals were then genotyped for common polymorphisms in P450 CYP2C8, P450 CYP2C9, UDP-glucuronosyl transferase (UGT)1A6 and peroxisome proliferator-activated receptor isoforms delta and gamma (PPARdelta and PPARgamma). Our study confirmed the reduction in risk of colorectal cancer with regular NSAID use (odds ratio (OR) = 0.73, 95% confidence interval (CI) (0.56, 0.95)) but showed that none of the polymorphic genes studied appeared to modify the protective effect of regular NSAID use.