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Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Departments of ¹ Epidemiology and ² Nutrition, School of Public Health, ³ Department of Medicine and Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and ⁴ Amgen, Inc., Thousand Oaks, California

Requests for reprints: Robert S. Sandler, Department of Medicine and Center for Gastrointestinal Biology and Disease, School of Medicine, CB#7555, 4111 Bioinformatics Building, University of North Carolina, Chapel Hill, NC 27599-7555. Phone: 919-966-0090; Fax: 919-966-2478. E-mail: robert_sandler{at}med.unc.edu

Objective: Decreased apoptosis in the colon is potentially an early indicator of colon cancer risk and may be influenced by calcium and vitamin D. This report describes the associations of calcium intake and 25-hydroxyvitamin D levels with apoptosis in colorectal epithelium.

Methods: Consecutive patients undergoing colonoscopies were recruited for a study designed to examine risk and etiologic factors for colorectal adenomas. Diet was assessed by food frequency questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were measured using an enzyme immunoassay. Apoptosis was scored from normal rectal mucosal pinch biopsies. Linear and logistic regression analyses were used to examine associations between calcium, serum vitamin D, and apoptotic scores. Data were available for 498 and 280 patients for the calcium and vitamin D analyses, respectively.

Results: Associations of calcium intake and vitamin D with apoptosis were modified by adenoma case-status. In an adjusted logistic regression model, patients with adenomas in the highest versus lowest tertile of dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI), 0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the highest level of 25-hydroxyvitamin D was associated with higher apoptosis in adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2).

Conclusion: These results are consistent with a calcium and vitamin D-mediated apoptotic mechanism in colon carcinogenesis.

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