Current issues of ACP Journal Club are published in Annals of Internal Medicine


Etiology

Regular aspirin use was associated with a decreased risk for colorectal cancer

ACP J Club. 1994 Nov-Dec;121:81. doi:10.7326/ACPJC-1994-121-3-081


Source Citation

Giovannucci E, Rimm EB, Stampfer MJ, et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994 Aug 15;121:241-6.


Abstract

Objective

To determine whether regular aspirin use was associated with decreased risk for colorectal cancer and adenoma in a cohort of male health professionals.

Design

6-year cohort study of men in the Health Professionals Follow-up Study.

Setting

Community-based study.

Participants

51 529 male health professionals responded to a mailed questionnaire in 1986. 3629 men were excluded from the analysis because of incomplete questionnaires and previous cancer. 47 900 men (mean age 57 y, range 40 to 75 y) were followed to diagnosis of colorectal cancer, death from other causes, or to the end of the study. Follow-up questionnaires were completed in 1988, 1990, and 1992. Participants were categorized as taking aspirin ≥ 2 times/wk, taking acetaminophen ≥ 2 times/wk, taking other anti-inflammatory medications, or as being nonusers.

Assessment of risk factors

Participants were asked about age, current and previous smoking, weight and height, family history of colorectal cancer, physical activity, and dietary and alcohol intake. Follow-up questionnaires inquired whether colorectal cancer had been diagnosed and asked about history of colonoscopy and sigmoidoscopy before and during the study and indications for endoscopy.

Main outcome measures

Relative risk (RR) for colorectal cancer.

Main results

Between 1986 and 1992, aspirin users had a lower risk for colorectal cancer than did nonusers (RR 0.70, 95% CI 0.53 to 0.92), and the inverse association grew stronger with consistent use during the 2 follow-up periods of 1988 to 1992 and 1990 to 1992 (RR 0.54, CI 0.35 to 0.83 and RR 0.38, CI 0.18 to 0.78, respectively). The risk for metastatic or fatal cancer was further reduced (RR for period between 1986 and 1992 0.52, CI 0.32 to 0.84). Aspirin-induced gastrointestinal bleeding leading to earlier diagnosis and removal of adenomas was unlikely to have influenced the inverse association between aspirin use and reduced risk for colorectal cancer because fewer adenomas were detected in aspirin users than in nonusers (5.6% vs 8.1%).

Conclusions

Regular aspirin use (≥ 2 times/wk) was associated with a decreased risk for colorectal cancer. Consistent aspirin use further reduced the risk.

Sources of funding: National Institutes of Health and the American Cancer Society.

For article reprint: Dr. E. Giovannucci, Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, 180 Longwood Avenue, Boston, MA 02115, USA. FAX 617-731-1541.


Commentary

Growing evidence exists that the humble aspirin may prevent colorectal cancer. Experimental studies in animals and observational studies in humans are remarkably consistent in showing a protective effect. Nonsteroidal anti-inflammatory agents have led to polyp regression in clinical trials in patients with familial polyposis.

The observational study by Giovannucci and colleagues extends our knowledge about the potential chemopreventive properties of aspirin. The strengths of the study include its large size, prospective design, complete follow-up, control for potential confounding factors, assessment of aspirin use at multiple time periods, and comprehensive analyses. The study showed an inverse association between duration of aspirin use and cancer incidence (dose response) that is not likely because of chance. The effect on metastatic and fatal cancers was especially strong, suggesting that aspirin could have a major effect on cancer deaths. A few limitations of the study were that it did not include women, the precise doses of aspirin were unknown, and not all members of the cohort were examined. It is conceivable that aspirin may slow the growth of cancers rather than actually prevent them (chemoprocrastination). Continued follow-up of the cohort will be informative.

Aspirin is inexpensive, available without prescription, and relatively safe. Based on reports in the lay press, many patients will take it on their own. When they seek our recommendations, we should try to stick to the facts. Aspirin may prevent colorectal cancer in men and women, but this is still unproven. Ongoing randomized trials of aspirin will provide us with more complete information on dose, adverse effects, and overall benefits on the colon and other organs.

Robert S. Sandler, MD, MPH
University of North CarolinaChapel Hill, North Carolina, USA