The chemoprevention of lung cancer using nonsteroidal anti-inflammatory drugs (NSAIDs)

A number of chronic inflammatory conditions are associated with increased risks of cancer. One of the key features of chronic inflammation is over-expression of the inducible enzyme, cyclooxygenase-2 (COX-2), which is responsible for conversion of arachidonic acid into molecular mediators of inflammation called prostaglandins. A host of recent studies suggest that COX-2 and its byproducts play a role in the development of certain types of cancer. Epidemiologic investigations have consistently shown that regular use of COX-2-inhibiting, non-steroidal anti-inflammatory drugs (NSAIDs) decreases the risk of colon cancer and breast cancer, and selective studies have noted NSAID-associated risk reductions for several other malignancies. However, one major type of cancer that has not been thoroughly investigated for NSAID effects is lung cancer.; To better understand the effect of regular use of NSAIDs on lung cancer development we undertook a case-control study of lung cancer, matching cases and controls for pack-years of cigarette smoking, as well as age and gender. In all, data for 384 cases from the Arthur G. James Cancer Hospital (Ohio State University, Columbus, Ohio) and 384 controls, comprising, participants, in cancer screenings, (breast and prostate) at the same institute were compiled for study. Using the methods of logistic regression, we observed an overall protective effect for NSAIDs against the development of lung cancer (adjusted OR = 0.52, 95% CI = 0.38–0.72). A decrease in risk was observed in both men (adjusted OR = 0.58; 95% CI = 0.38–0.87) and women (adjusted, OR = 0.44, 95% CI = 0.26–0.74). Likewise, significant protective effects of NSAIDs were observed for squamous cell carcinoma (adjusted OR = 0.56, 95% CI = 0.34–0.93) and large cell carcinoma (adjusted OR = 0.32, 95% CI = 0.14–0.72), and a suggestive effect was present for adenocarcinoma (adjusted OR = 0.68; 95% CI = 0.43–1.07). There was also a significant dose response of decreasing relative risk with amount of NSAID use (trend test, p < 0.001). These results point to possible chemopreventive effects of NSAIDs against lung cancer in cigarette smokers and suggest a need for further molecular and clinical investigations of the role of COX-2 in lung carcinogenesis.