Long-term aspirin use and cancer risk: a 20-year cohort study

Background: Long-term use of aspirin has been shown to reduce colorectal cancer risk, but the association remains inconclusive for individual noncolorectal cancers. We examined the association between long-term aspirin use and cancer risk in Denmark.

Methods: Using nationwide registries, we followed individuals aged 40-70 years at baseline (January 1, 1997) for cancer diagnoses through 2018. We assessed low-dose (75-150 mg) aspirin use according to continuity, duration, and cumulative amount. In addition, we explored associations with consistent high-dose (500 mg) aspirin use. Using Cox regression, we estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) with aspirin use for overall and site-specific cancer.

Results: Among 1 909 531 individuals, 422 778 were diagnosed with cancer during mean follow-up of 18.2 years. Low-dose aspirin use did not reduce the hazard ratio for cancer overall irrespective of continuity and duration of use (continuous use: HR = 1.04, 95% CI = 1.03 to 1.06). However, long-term (≥5 or ≥10 years) use was associated with at least 10% reductions in hazard ratios for several cancer sites: colon, rectum, esophagus, stomach, liver, pancreas, small intestine, head and neck, brain tumors, meningioma, melanoma, thyroid, non-Hodgkin lymphoma, and leukemia. Substantially elevated hazard ratios were found for lung and bladder cancer. In secondary analyses, consistent high-dose aspirin use was associated with reduced hazard ratios for cancer overall (HR = 0.89, 95% CI = 0.85 to 0.93) and for several cancer sites.

Conclusion: Long-term low-dose aspirin use was associated with slight to moderately reduced risks for several cancers but not for cancer overall owing to increased risk for some common cancers. Similar or slightly stronger inverse associations were observed for consistent use of high-dose aspirin.