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Background: Prior epidemiological and intervention studies have not been able to separate independent effects of dose, timing and duration of aspirin use in colorectal cancer (CRC) chemoprevention. We examined aspirin-based CRC chemoprevention according to timing in the Nurses’ Health Study and Health Professionals Follow-Up Study.
Methods: The exposures include cumulative average dose and total duration of aspirin use in > 10 years before follow-up started (remote period), and in the immediate 10 years before follow-up started (recent period). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals for exposures and CRC risk.
Results: Aspirin use >10 years before follow-up started (HR = 0.88, 95% CI = 0.83 to 0.94) per 5 year increment) and immediate 10 years before follow-up started (HR = 0.90, 95% CI = 0.84 to 0.96) were similarly important in CRC chemoprevention, though a 5-year lag was required for a clear benefit in the recent period. In the remote period, the association was not dose-dependent; compared to < 0.5 standard (325 mg)-dose tablets/week; hazard ratios were HR = 0.78, 95% CI = 0.63 to 0.98, HR = 0.81, 95% CI = 0.72 to 0.91, and HR = 0.74, 95% CI = 0.64 to 0.86 for doses of 0.5 to < 1.5, 1.5 to < 5, ≥5 tablets/week, respectively. However, there was dose dependency in the recent period (with respective HR = 0.91, 95% CI = 0.79 to 1.06; HR = 0.87, 95% CI = 0.77 to 0.98; and HR = 0.76, 95% CI = 0.64 to 0.91).
Conclusion: A suggestive benefit necessitates at least 6–10 years and most clearly after approximately 10 years since initiation of aspirin. Remote use and use within the previous 10 years both contribute independently to decreased risk, though a lower dose may be required for a benefit with longer term use.
Edward L Giovannucci
Yin Zhang,Andrew T Chan,Jeffrey A Meyerhardt,Edward L Giovannucci