Nonsteroidal anti‐inflammatory drugs and other analgesic use and bladder cancer in northern New England

Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are among the most commonly used over-the-counter medications in the United States.1 Among adults 20 years of age or older, the lifetime prevalence of daily use for 1 month or more is approximately 10, 7 and 5% for NSAIDs, aspirin and acetaminophen, respectively.1,2 NSAIDs, including selective cyclooxygenase (COX-2) inhibitors, have been investigated as cancer chemopreventive agents in experimental and observational studies.3,4 The antitumor properties of NSAIDs are thought to be attributable to their capacity to inhibit the COX-2 enzyme, inhibit proliferation, and induce apoptotic cell death5,6; however, other COX-independent pathways may also contribute to the antitumor characteristics of these agents.4,7,8 A number of epidemiologic studies have examined the association between use of NSAIDs and bladder cancer risk. Three case–control studies have observed associations for several classes of NSAIDs with reduced risk of bladder cancer; however, the strength of the association varies by formulation.9–11 One cohort study reported increased risk,12 two had null findings13,14 and a recent pooled analysis of three large cohort studies suggested a significant protective effect among nonsmokers who reported daily use of nonaspirin NSAIDs.15 The effects of regular intake of selective COX-2 inhibitors on bladder cancer risk have not been studied extensively, because these drugs were introduced to the market in the 1990s.3 The primary goal of this large, population-based case–control study was to determine the reasons for the persistently elevated mortality and incidence rates of bladder cancer among men and women in northern New England.16 In this context, we evaluated use of NSAIDs and analgesics and bladder cancer risk in northern New England based on a detailed assessment of drug composition and dose, obtained through in-person interviews. We also evaluated effect modification by 39 candidate genes in the NSAID metabolism pathway for ibuprofen, a commonly used drug for which we observed the strongest main effect.