Use and safety of aspirin in the chemoprevention of colorectal cancer.

Colorectal cancer is the third leading cause of cancer-related mortality and a significant public health problem in the United States. Aspirin and other nonsteroidal anti-inflammatory drugs reduced the incidence of colorectal cancers and related mortality by 30% to 60% as well as the incidence of colonic adenomas. This effect is presumably due to an inhibition of cyclooxygenase 2, an inducible enzyme involved in the synthesis of prostaglandins. Prostaglandins are increased in colorectal neoplasms. Aspirin's effect appears to be dose related and enhanced by long-term exposure. Two prospective studies, however, failed to show a protective benefit of aspirin in colorectal cancer. When used long term, aspirin has significant adverse effects and is poorly tolerated. The gastrointestinal toxicity of aspirin is dose related, but even low doses of aspirin (75 mg per day) when used regularly result in significantly higher gastrointestinal toxicity, manifested by melena, hematemesis, and peptic ulcer disease, in aspirin users compared with nonusers. Furthermore, some studies indicate an increased risk of hemorrhagic strokes in aspirin users. Presently, aspirin should not be recommended for the primary chemoprevention of colorectal cancer in the general population due to significant risks of serious cerebrovascular and gastrointestinal adverse effects associated with long-term aspirin use.