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Background and Methods. Experiments in animals and two epidemiologic studies in humans suggest that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may be protective against colon cancer. We tested this hypothesis in a prospective mortality study of 662,424 adults who provided information in 1982 on the frequency and duration of their aspirin use. Death rates from colon cancer were measured through 1988. The possible influence of other risk factors for colon cancer was examined in multivariate analyses for 598 case patients and 3058 matched control subjects drawn from the cohort.

Results. Death rates from colon cancer decreased with more frequent aspirin use in both men and women. The relative risk among persons who used aspirin 16 or more times per month for at least one year was 0.60 in men (95 percent confidence interval, 0.40 to 0.89) and 0.58 in women (95 percent confidence interval, 0.37 to 0.90). The risk estimates were unaffected when we excluded persons who reported at entry into the study that they had cancer, heart disease, stroke, or another condition that might influence both their aspirin use and their mortality. Adjustment for dietary factors, obesity, physical activity, and family history did not alter the findings significantly. No association was found between the use of acetaminophen and the risk of colon cancer.

Conclusions. Regular aspirin use at low doses may reduce the risk of fatal colon cancer. Whether this is due to a direct effect of aspirin, perhaps mediated by the inhibition of prostaglandin synthesis, or to other factors indirectly associated with aspirin use is unclear. (N Engl J Med 1991;325:1593-6.)

: NONSTEROIDAL antiinflammatory drugs (NSAIDs), such as aspirin, indomethacin, piroxicam, and sulindac, inhibit the growth of colon tumors induced by chemical carcinogens in rodents.1 2 3 4 5 6 7 8 9 10 11 12 13 The mechanism is unknown, but it may involve the suppression of cell proliferation or the stimulation of an immune response, due to an inhibitory effect on prostaglandin synthesis.14 15 16 17 18 A similar effect in humans has been suggested by case reports and by a small randomized clinical trial describing the regression of large-bowel polyps in patients with familial polyposis treated with sulindac.19 20 21

Three recent epidemiologic studies have examined the occurrence of cancer of the colon or rectum in humans [horizontal ellipsis]

Owned, published, and (C) copyrighted, 1991, by the MASSACHUSETTS MEDICAL SOCIETY