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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.

Type

Journal article

Journal

The Netherlands journal of medicine

Publication Date

04/2009

Volume

67

Pages

134 - 141

Addresses

Department of Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam, the Netherland.

Keywords

Humans, Colorectal Neoplasms, Aryl Hydrocarbon Hydroxylases, Anti-Inflammatory Agents, Non-Steroidal, Proportional Hazards Models, Risk Factors, Prospective Studies, Genotype, Alleles, Aged, Aged, 80 and over, Middle Aged, Netherlands, Female, Male