Cited 1 times since 2009 (0.1 per year) source: EuropePMC The Netherlands journal of medicine, Volume 67, Issue 4, 1 1 2009, Pages 134-141 No modification of the beneficial effect of NSAIDs on colorectal cancer by CYP2C9 genotype. Siemes C, Eijgelsheim M, Dieleman JP, van Schaik RH, Uitterlinden AG, van Duijn CM, Hofman A, Coebergh JW, Stricker BH, Visser LE
Background
CYP2C9 enzymes are involved in non-steroidal anti-inflammatory drug (NSAID) metabolism. Therefore, we investigated whether CYP2C9*2 and *3 variant alleles, encoding for enzymes with lower activity, increased the protective effect of NSAIDs on colorectal cancer.
Methods
Individual and combined associations of NSAIDs and CYP2C9*2 and *3 variant alleles with colorectal cancer were studied in 7757 Caucasian individuals of The Rotterdam Study, a population-based prospective cohort since 1990. Additive and multiplicative effect modification models were used to examine drug-gene interactions.
Results
There were 212 incident cases of colorectal cancer during follow-up. A reduced risk of colorectal cancer was observed in individuals who used NSAIDs for more than a year (HR 0.45; 95% CI 0.28 to 0.71), and in carriers of an CYP2C9 variant allele associated with lower enzymatic activity (HR 0.67; 95% CI 0.47 to 0.96). The combination of both determinants was associated with a further risk reduction but without synergy.
Conclusion
Both NSAID use and CYP2C9*2 and/ or *3 carriage are associated with a reduced risk of colorectal cancer. However, no interaction between the determinants was found, which might indicate independent pathophysiological mechanisms.
