Background: To date, calcium has been the only dietary substance shown to be chemopreventive against colorectal neoplasia in a large clinical trial. The present study evaluates the duration of this protective effect beyond the cessation of active supplementation. Methods: In the Calcium Polyp Prevention Study, 930 eligible subjects were randomized to receive either placebo or 1200 mg of elemental calcium daily for 4 years. Two study colonoscopies were scheduled at 1 and 4 years after enrollment. The last subject completed active treatment in February 1997. The Calcium Follow Up Study was designed as an observational phase to track adenoma occurrence after the end of randomized treatment as well as the use of medications, vitamins and supplements during that time. The first of 5 annual questionnaires was requested in January of 1999, 2 to 7 years after the end of study treatment. We obtained follow-up information from 822 of 865 living subjects. Of these, 597 underwent a colonoscopy six or more months after the final study exam. Our endpoint in this analysis was the occurrence of adenomas, hyperplastic polyps and advanced adenomas in the first post-treatment exam within 6 months to five years after cessation of randomized study treatment. In addition to estimating the duration of the treatment effect, we assessed the association of calcium supplement use during the follow up period with adenoma risk. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CI) with adjustment for age, sex, study center and interval between the final study exam and the first follow up colonoscopy. Results: In an intention-to-treat analysis, the risk of adenomas was significantly lower among calcium subjects during the five-year period following the final study exam (adjusted RR 0.72, 95% CI 0.53-0.98). There was an even larger effect for hyperplastic polyps (adjusted RR 0.53, 95% CI 0.30-0.92). The association for advanced adenomas was null. Broadly similar findings were seen among subjects who did not use calcium supplements after study treatment ended. However, supplement use during the follow up phase conferred a non-significant reduction in adenoma risk that was similar to that seen during the active phase of the trial (adjusted RR 0.85, 95% CI 0.62-1.18). In an analysis that extended up to 10 years after the end of active supplementation, the original study treatment allocation was not associated with the risk of any type of polyp. Conclusion: The protective effect of calcium supplementation on colorectal polyps seems to extend up to 5 years after cessation of active treatment.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]