Women who took two or more aspirin or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) per week for more than 10 years significantly reduced their risk of colorectal cancer, according to an article in the August 24/31 issue of JAMA, the Journal of the American Medical Association.

At the same time though, the researchers said there is a downside to substantially higher doses of aspirin than currently recommended for the prevention of cardiovascular disease.

Recent randomized intervention trials have demonstrated that regular use of aspirin in patients with a history of colorectal adenoma (benign tumor) or cancer reduces the risk of recurrent adenoma within 1 to 3 years. But, whether long-term use of aspirin similarly reduces the risk of colorectal cancer and, if so, at what dose, has been unclear.

Andrew T. Chan, M.D., M.P.H., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined the influence of aspirin and NSAIDs on the risk of colorectal cancer in a large group of women. The study included 82,911 women, enrolled in the Nurses' Health Study, who have been providing data on medication use biennially since 1980 and followed up through June 1, 2000.

Over the 20-year period, 962 cases of colorectal cancer were documented. Among women who regularly used aspirin (2 or more standard [325-mg] tablets per week), there was a 23 percent reduced relative risk for colorectal cancer compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use.

The benefit appeared related to dose: compared with women who reported no use, the relative risk for cancer was 10 percent greater for women who used 0.5 to 1.5 standard aspirin tablets per week; 11 percent lower with 2 to 5 aspirin per week; 22 percent lower with 6 to 14 aspirin per week; and 32 percent lower with more than 14 aspirin per week.

Women who took more than 14 aspirin per week for longer than 10 years had a 53 percent lower relative risk for colorectal cancer. A similar dose-response relationship was found for nonaspirin NSAIDs.

The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week.

"Our study supports a possible role for aspirin in cancer prevention, which has been demonstrated by prior adenoma recurrence trials. However, any substantial impact of aspirin on cancer necessitates early initiation and prolonged, consistent use. Many toxicities of aspirin, including gastrointestinal bleeding, are dose-dependent. Thus, future studies will need to thoroughly consider the risk-benefit profile for aspirin/NSAID chemoprevention among various risk groups and compare such a strategy with other potential prevention efforts," the authors conclude.