Long-term NSAID use and incident urothelial cell carcinoma in the VITamins and Lifestyle (VITAL) study.

PURPOSE: Literature on the chemopreventive role of nonsteroidal anti-inflammatory drugs (NSAIDs) in urothelial carcinoma of the bladder (UC) is conflicting. A recent pooled analysis of 3 cohorts reported regular use of nonaspirin NSAIDs was associated with reduced risk of urothelial carcinoma (UC) among nonsmokers only; however, nonsmokers are a group with a low risk of UC. We examine the association between NSAID use and UC risk.

MATERIALS AND METHODS: Study participants were members of the VITamins and Lifestyle (VITAL) cohort of 77,048 Washington State residents aged 50-76 years who completed a baseline questionnaire in 2000-2002 on NSAID use and cancer risk factors. Ten-year use of aspirin and other NSAIDs was categorized as none, low-use (1-3 d/wk or <4 years), or high-use (≥ 4 d/wk and ≥ 4 years). Incident UC cases were prospectively identified via linkage to a local cancer registry. Hazard ratios (HR) were estimated by multivariate Cox regression.

RESULTS: A total of 385 incident cases of UC were diagnosed over a mean follow-up of 7 years. There was no association with NSAID use and risk of UC. However, the association of use of nonaspirin NSAIDs with UC risk differed by smoking status (P for interaction = 0.02). Specifically, among long-term former smokers (quit ≥ 10 years), nonaspirin NSAID use was associated with a 31% reduction in risk of UC in low-users (HR 0.69, 95% CI 0.46-1.04), and 48% reduction in risk for high-users (HR 0.52, 95% CI 0.24-1.11, P for trend = 0.02).

CONCLUSIONS: Our results show a risk reduction with nonaspirin NSAID use among long-term quitters, a group with significant risk of UC.