Colorectal cancer after start of nonsteroidal anti-inflammatory drug use.

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently shown to reduce the risk of colorectal cancer (CRC) in non-experimental studies, but little is known of the factors associated with starting and continuing regular NSAID use and their effect on the NSAID and CRC association.

Subjects And Methods: We performed a prospective cohort study of 22,071 healthy male physicians aged 40 to 84 years without indications or contraindications to regular NSAID use at baseline. Annual questionnaires assessed quantity of NSAID use, occurrence of cancer, and risk factors for CRC. Propensity for regular NSAID use (>60 days/year) was estimated using generalized estimating equations. We used a time-varying Cox proportional hazards model to estimate the association between duration since initiation of regular NSAID use and risk for CRC.

Results: Regular non-aspirin and any NSAID use increased from 0% to 12% and 1% to 56% over time, respectively and was predicted by age, body mass index, alcohol consumption, medication use, coronary artery disease, gastrointestinal diseases, arthritis, hypertension, and headaches. Over a median follow-up of 18 years, 495 physicians were diagnosed with CRC. There was no trend of CRC risk with increased duration of regular NSAID use. Five or more years of regular use of any NSAID were associated with a relative risk for CRC of 1.0 (95% confidence interval: 0.7-1.5), after adjustment for predictors of regular NSAID use.

Conclusion: Regular NSAID use was not associated with a substantial risk reduction of CRC after controlling for time-varying predictors of both NSAID use and CRC.