Aspirin, Prostaglandins, and Colon Cancer

ABSTRACT & COMMENTARY

Synopsis: High levels of prostaglandins are observed in colon cancer tissues. A single, daily dose of 81 mg of aspirin appears to be the optimal regimen as a chemo-preventive agent for colorectal cancer.

Source: Ruffin MT, et al. J Natl Cancer Inst 1997;89:1152-1160.

Colon cancer is the second most common cancer in both men and women who don’t smoke, surpassed only by breast cancer in women and prostate cancer in men. There are 130,000 cases of colon cancer per year in the United States. Colon cancer starts in polyps. Prevent polyps either at initiation or through removal once established, and cancer is prevented.1

Numerous studies have shown that many nonsteroidal antiinflammatory drugs, including aspirin, prevent polyp formation and, subsequently, colorectal cancer.2 Initially, it was thought that the higher the dose of aspirin, the more protective the effect. However, with higher dosages come complications of gastric bleeding and GI upset.

Sixty-five subjects over 18 years of age were given varying doses of aspirin (placebo, 40.5, 81, 162, 324, or 648 mg) for 14 days. Colorectal biopsy specimens were taken at baseline, 24 hours after the first dose, and 72 hours after the fourteenth dose. They were assayed for prostaglandins. Although no detectable amounts of acetylsalicylic acid or salicylic acid were present in the plasma at any of the biopsy time points, prostaglandins remained significantly suppressed in colorectal mucosa at 72 hours after the 81 mg dose.

COMMENT BY JOHN L. PFENNINGER, MD

This study confirms an earlier pilot study showing that colorectal mucosal tissue maintains a significant anti-prostaglandin level long after NSAIDs have cleared from the serum. Not only is aspirin protective for atherosclerotic vascular disease and its complications, it is also protective for colorectal cancer.

If aspirin were developed today, it would be a miracle drug and sell for an exorbitant amount. Because it is a common OTC medication, it is disregarded not only by patients, but also by physicians themselves.

Without significant contraindications, each of us should be recommending that our patients take 81 mg (a baby aspirin or one-fourth of an adult aspirin) daily. Research has yet to define the age at which this recommendation should be implemented. It has been estimated that up to 50% of colorectal carcinomas could be eliminated.

The United States Preventative Comments Services Task Force (USPSTF) has now also endorsed the recommendation of regular screening in asymptomatic individuals with flexible sigmoidoscopy beginning at 50 years of age.3 Until 1995, the American Academy of Family Physicians (AAFP) and USPSTF were the only two significant groups withholding this recommendation "based on available scientific evidence."

Colon cancer prevention needs a strong emphasis similar to the efforts we have expended for breast, cervical, and prostate cancer detection and prevention. Not only must we emphasize the traditional "high bulk diet," we can be more specific. Five helpings of fruits and vegetables per day are essential. Smoking must be stopped and alcohol limited. (Both increase colorectal cancer alone and are synergistic together.) Estrogen replacement lowers colon cancer risk.4 Now, we must emphasize daily aspirin use and regular sigmoidoscopy screening. We are making progress. (Dr. Pfenninger is President and Director, The National Procedures Institute, Midland, MI.)

References

1. Winawer SJ, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Work Group. N Engl J Med 1993;329:1977-1981.

2. Thun MJ, et al. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 1991;325:1593-1596.

3. United States Preventive Tasks Force. Guide to Clinical Preventive Services, 2nd ed. Baltimore, MD: Williams & Wilkins; 1996.

4. Calle EE, et al. Estrogen replacement therapy and risk of fatal colon cancer in a prospective client of postmeno-pausal women. J Natl Cancer Inst 1995;87:517-523.