Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract. Extent, mode, and dose dependence of anticancer effects.

Regular intake of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased incidence of colorectal, esophageal, gastric, and lung cancer. The relative risk of colorectal cancer is about 0.6 in large cohort studies--in other words, the risk is reduced by 40%. Also, in experimental models, the frequency of colonic cancer is reduced by NSAIDs. Both human and experimental tumors contain increased amounts of prostaglandin E(2), which may have a role in the accelerated proliferation taking place in tumor tissue. This may be the result of activation of cyclooxygenase-2 (COX-2) in response to mitogens and growth factors, for example, which will result in an increased production of prostaglandins. The current theory is that the mechanism for the suppressor effect of NSAIDs on carcinogenesis is COX-2 inhibition. However, reliable data on the dose of aspirin or other NSAIDs for optimal benefit for tumor suppression are lacking, and it is still premature to give general recommendations on using NSAIDs for chemoprevention of gastrointestinal cancer.