Evidence supports the use of short- or long-term aspirin therapy in reducing the risk of colorectal adenoma and cancer. The optimal dosage and the true duration needed for primary cancer prevention are uncertain. The target population among whom primary prevention will be beneficial remains another question.

Chan and associates looked at the women in the Nurses’ Health Study to examine the relationship between aspirin and colorectal adenoma. These registered nurses have been followed for more than 20 years with detailed questionnaires on risk factors for cancer and coronary heart disease. The authors studied the effect of aspirin use in women who underwent colonoscopy or sigmoidoscopy. Of these women, 1,368 had confirmed distal colorectal adenoma, and 25,709 had no confirmed distal colorectal adenoma.

Among the women with confirmed distal colorectal adenoma, 38 percent were regular aspirin users who took two or more standard aspirin tablets weekly. The incidence of adenomas was significantly lower among regular aspirin users. The benefit of aspirin was substantially higher with increasing dosage. Women who took more than 14 tablets per week had the greatest risk reduction. There appeared to be no greater benefit among more consistent aspirin users who had continued aspirin therapy for longer periods of time. The effect of aspirin was not influenced by age, family history of colorectal adenoma, or use of postmenopausal hormones. In a secondary analysis that looked at proximal adenoma occurrence, regular use of aspirin was again associated with decreased risk.

The authors conclude that regular aspirin use is associated with a 25 percent reduction in the risk of sporadic, colorectal adenomas in an average-risk population. Women who take more than 14 regular aspirin tablets weekly have the greatest risk reduction. This aspirin benefit is noted among short-term (less than five years) and long-term (more than five years) users. Because the dosage for chemoprophylaxis would be substantially higher than that recommended for prevention of cardiovascular disease, the risk-benefit profile must be evaluated futher before the higher doses of aspirin for adenoma prophylaxis can be widely recommended.

In an editorial in the same journal, Sandler supports these conclusions. He suggests that aspirin be used only in persons at higher risk for adenomas who do not have risk factors for aspirin complications. Colonoscopy remains essential for screening among low-and high-risk patients, regardless of aspirin use.

editor’s note: Colorectal cancer is the second highest cause of cancer mortality in western developed countries. Screening is currently our best method of reducing mortality, but compliance with widespread screening has been less than desired. Biomarkers are being studied but are not yet clinically useful. Prevention would be an important health care advance. The risk of adenomas does not appear to be associated with low consumption of folate, but rather with low intake of fiber. Nonsteroidal anti-inflammatory drugs, including aspirin, sulindac, and celecoxib, inhibit colorectal carcinogenesis by suppressing adenomatous polyp development and causing regression of existing polyps in patients with familial adnenomatous polyposis. This appears to be true even in persons with advanced polyps.¹ Suggested mechanisms for this action include induction of apoptosis in neoplastic cells or cell cycle regulation by altered protein expression.—r.s.