CALCIUM AND COLORECTAL EPITHELIAL CELL PROLIFERATION

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Promising, but as yet inconclusive evidence has been accumulating to indicate that dietary calcium in sufficient quantity, may be a protective factor against colorectal cancer--particularly for those consuming typical high fat Western-style diets. Evidence now also exists to support colonic epithelial cell proliferation as indicated by tritiated thymidine [3H]dTh - labeling of the cells as a biomarker or potential precursor lesion for colonic polyps and colonic cancer. These cells which can be obtained for study by simple non-prep rectal biopsies reflect risk for neoplasia that has occurred higher in the colon. Furthermore, evidence now also exists that this hyperproliferation in the colonic mucosa can be reversed by administration of calcium supplementation and the risk of colonic cancer thereby reduced. To date three uncontrolled trials on the effect of calcium on colonic epithelial cell proliferation in humans have been conducted. All three have shown important reductions. However, to date no randomized controlled trials or trials utilizing different dosages have been reported. Furthermore, there has been no serial or long term follow-up of the effect of calcium on colonic epithelial cell proliferation to determine how quickly a full benefit is achieved or whether or not an adaptive process may occur which would lessen the effect over time. Also, at this point, little is known regarding the possible natural fluctuation of colonic epithelial cell proliferation in high risk humans with previous colonic adenomatous polyps. This proposed randomized double-blind placebo-controlled clinical trial would address these gaps by having a control group (which performs a dual function of also being a high risk natural history group), having two different calcium supplementation level groups and by following up each group with rectal biopsies at three different times. This study therefore will provide needed data on the relationship between calcium and colonic epithelial cell proliferation, adenomatous polyps and colonic cancer. This study will also provide a basis for further studies of the value of colonic epithelial cell proliferation as a biomarker of subsequent development of colonic polyps and colonic cancer and for other dietary interventions on this marker including the evaluation of dietary interactions such as those of calcium with fat, vitamin D3, and fiber.