Aspirin and other nonsteroid anti-inflammatory drugs as cancer-preventive agents

Several lines of evidence support the notion that aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs) may prevent human cancer, particularly cancers of the large bowel. These drugs are potent inhibitors of cyclo-oxygenases, enzymes that catalyse the synthesis of prostaglandins from arachidonic acid. In rodent models, NSAIDs consistently inhibit chemically induced neoplasms of the colorectum. Case reports and randomized controlled trials are also consistent in showing a reduction in adenomas following administration of the NSAID sulindac to patients with familial adenomatous polyposis. Perhaps the most intriguing evidence, however, comes from epidemiological studies, which indicate a 30-50% reduction in risk of colorectal neoplasia among regular users of aspirin. These studies have employed both case-control and cohort approaches, and lower risk has been found for colon and rectal cancer mortality, invasive cancer incidence, and adenoma occurrence. The results of the epidemiological studies are not uniform, however, and a few studies found no benefit with aspirin use. Existing epidemiological studies are limited by a lack of information about dosage and duration of aspirin use. Moreover, questions remain about the mechanism through which NSAIDs might affect cancer occurrence. Thus, there is a clear need for focused clinical trials, as well as for further epidemiological study and laboratory investigation, to define better the potential of these agents to prevent cancers.