Randomized trials of short-term Aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a relationship between Aspirin and colorectal neoplasia.
However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with Aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) remain limited.

Researchers at the Massachusetts General Hospital and Harvard Medical School, Boston, examined the influence of Aspirin and NSAIDs in prevention of colorectal cancer.

Prospective cohort study of 82 911 women enrolled in the Nurses' Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000.

Over a 20-year period, 962 cases of colorectal cancer were documented.

Among women who regularly used Aspirin ( > or =2 standard [ 325-mg ] tablets per week ), the multivariate relative risk ( RR ) for colorectal cancer was 0.77 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 multivariate RRs for cancer were 1.10 for women who used 0.5 to 1.5 standard Aspirin tablets per week, 0.89 for 2 to 5 Aspirin per week, 0.78 for 6 to 14 Aspirin per week, and 0.68 for more than 14 Aspirin per week.
Women who used more than 14 Aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47.
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.

The results of this study showed that a significant benefit of Aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week.

Optimal chemoprevention for colorectal cancer requires long-term use of Aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered.

Source: Journal of the American Medical Association, 2005


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