BACKGROUND & AIMS: Long-term data on the risk of colorectal cancer according to dose, duration, and consistency of aspirin therapy are limited.

METHODS

We conducted a prospective study of 47,363 male health professionals who were ages 40-75 years at enrollment in 1986. Biennially, we collected data on aspirin use, other risk factors, and diagnoses of colorectal cancer. We confirmed all reports of colorectal cancer through 2004 by review of medical records.

RESULTS

During 18 years of follow-up, we documented 975 cases of colorectal cancer over 761,757 person-years. After adjustment for risk factors, men who regularly used aspirin (>/=2 times per week) had a multivariate relative risk (RR) for colorectal cancer of 0.79 (95% confidence interval, [CI], 0.69-0.90) compared with nonregular users. However, significant risk reduction required at least 6-10 years of use (P for trend = .008) and was no longer evident within 4 years of discontinuing use (multivariate RR, 1.00; CI, 0.72-1.39). The benefit appeared related to increasing cumulative average dose: compared with men who denied any aspirin use, the multivariate RRs for cancer were 0.94 (CI, 0.75-1.18) for men who used 0.5-1.5 standard aspirin tablets per week, 0.80 (CI, 0.63-1.01) for 2-5 aspirin tablets per week, 0.72 (CI, 0.56-0.92) for 6-14 aspirin tablets per week, and 0.30 (CI, 0.11-0.81) for >14 aspirin tablets per week (P for trend = .004).

CONCLUSIONS

Regular, long-term aspirin use reduces risk of colorectal cancer among men. However, the benefit of aspirin necessitates at least 6 years of consistent use, with maximal risk reduction at doses greater than 14 tablets per week. The potential hazards associated with long-term use of such doses should be carefully considered.