Modulation of Abnormal Colonic Epithelial Cell Proliferation and Differentiation by Low-Fat Dairy Foods

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Abstract
Context.— Before the development of human colonic neoplasms, colonic epithelial cells showed altered growth and differentiation. These alterations characterized mucosa at risk for cancer formation and were termed intermediate biomarkers of risk. Modifications of the mucosa toward more normal features by nutrients or drugs are putative approaches to chemoprevention of colon cancer. Objective.— To determine whether increasing calcium intake via dairy products alters colonic biomarkers toward normal. Design.— Randomized, single-blind, controlled study. Setting.— Outpatient clinic. Participants.— Seventy subjects with a history of polypectomy for colonic adenomatous polyps. Intervention.— Low-fat dairy products containing up to 1200 mg/d of calcium. Subjects were randomized to 4 strata by diet (control vs higher calcium) and age (Main Outcome Measures.— Changes in total colonic epithelial cells and number and position of thymidine-labeled epithelial cells and changes in the ratio of sulfomucins (predominantly secreted by distal colorectal epithelial cells) to sialomucins and expression of cytokeratin AE1, 2 markers of colonic cell differentiation. Results.— During 6 and 12 months of treatment, reduction of colonic epithelial cell proliferative activity (P<.05), reduction in size of the proliferative compartment (P<.05), and restoration of acidic mucin (P<.02), cytokeratin AE1 distribution (P<.05), and nuclear size (P<.05) toward that of normal cells occurred. Control subjects showed no differences from baseline proliferative values at 6 and 12 months (P>.05). Conclusion.— Increasing the daily intake of calcium by up to 1200 mg via low-fat dairy food in subjects at risk for colonic neoplasia reduces proliferative activity of colonic epithelial cells and restores markers of normal cellular differentiation.