Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins And Lifestyle (VITAL) cohort

ObjectiveChronic inflammation may be an important factor in the initiation and promotion of endometrial cancer. Use of non-steroidal anti-inflammatory drugs (NSAIDs), however, has been inconsistently associated with endometrial cancer risk.Methods22,268 female residents of western Washington State, ages 50–76, completed a baseline questionnaire in 2000–2002 and reported on their use of individual NSAIDs over the past 10 years. Use was categorized as none, low (< 4 days/week or < 4 years), and high (≥ 4 days/week and ≥ 4 years). Over 9 years of follow-up, 262 incident invasive endometrial cancers were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsRelative to non-use, high use of aspirin was inversely associated with endometrial cancer risk (HR 0.64, 95% CI: 0.41–1.01; P trend = 0.03). Findings were stronger for regular-strength than low-dose aspirin. High use of non-aspirin NSAIDs (HR 1.15, 95% CI: 0.68–1.95), including ibuprofen (HR 1.29, 95% CI: 0.73–2.28), and naproxen (HR 1.08, 95% CI: 0.39–2.95) was not associated with risk. In subgroup analyses, findings for aspirin were strongest for cancers of endometrioid histology and were restricted to non-smokers.ConclusionsThis study provides additional evidence that use of aspirin, but not non-aspirin NSAIDs, may reduce the risk of endometrial cancer, especially in estrogen-mediated cases; however additional prospective studies with high-quality measurement of NSAID use are needed. Aspirin should continue to be examined as a potential agent for cancer chemoprevention.

► Existing studies of NSAIDs and endometrial cancer risk are inconsistent.
► In this cohort study, aspirin linearly reduced endometrial cancer risk.
► Individual non-aspirin NSAIDs were not associated with risk.