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Calcium Supplements Have Long-Term Benefit in Polyp Prevention

The preventive effect of calcium on colorectal adenoma recurrence continues for about 5 years after cessation of active supplementation.

Colorectal cancer is the third most common cancer in the U.S. and the second leading cause of cancer-related death. Because of its high incidence, the motivation is strong to develop treatments that prevent or reduce risk for colorectal cancer. Results from the Calcium Polyp Prevention Study (CPPS) showed that dietary calcium supplementation lowered risk for colorectal adenomas and polyps (N Engl J Med 1999; 340:101). In the CPPS, patients with histories of colorectal adenomas were assigned randomly to calcium supplementation (1200 mg of elemental calcium daily) or to placebo, and colonoscopy was performed at 1 year and 4 years. Calcium supplementation resulted in a 17% relative reduction in risk for developing recurrent adenomas and an even larger reduction in risk for developing more advanced adenomas.

However, what is the long-term effect of calcium supplementation on development of polyps? Researchers now report on the observational phase of the CPPS, with data on two consecutive 5-year intervals after completion of the 4-year active study period. Of 930 participants in the initial study, follow-up information was available for 822, and 596 underwent at least one colonoscopy after the end of randomized treatment. After study treatment ended, 196 patients continued to take some form of calcium supplementation. The average time to post-study colonoscopy was 5.9 years.

During the first 5 years of post-study follow-up, compared with placebo patients, patients who had been assigned to calcium supplements initially continued to show a marked reduction in risk for adenomas (43.2% vs. 31.5%; adjusted relative risk, 0.063; P=0.005); this lower risk did not apply to more advanced adenomas. However, during the subsequent 5-year interval, initial study treatment did not affect risk for adenomas (RR, 1.09; P=0.511).

Comment: The CPPS Follow-up Study results indicate that the preventive effect of calcium on colorectal adenoma recurrence continues for about 5 years after cessation of active supplementation. The results validate the use of calcium supplementation as a preventive strategy in patients with colorectal adenomas. The identification of this longer benefit of calcium supplementation represents a step forward in the field of colorectal cancer prevention. The strengths of the study include the initial placebo-controlled randomized trial design, the length of study follow-up, the relatively high adherence rate for follow-up colonoscopy, and the central review of pathology samples taken during colonoscopy. What this and other trials can’t tell us is the actual effect of supplementation on cancer development (rather than just adenoma recurrence), because patients with polyps continue to undergo active screening colonoscopies once adenomas are detected.

— David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology March 5, 2007

Citation(s):

Grau MV et al. Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst 2007 Jan 17; 99:129-36.

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