Effects of Vitamin D and Calcium Supplementation on Markers of Apoptosis in Normal Colon Mucosa: A Randomized, Double-blind, Placebo-controlled Clinical Trial

• Type of Material: Article
• Authors: Veronika Fedirko, Emory University; Roberd M Bostick, Emory University; W Dana Flanders, Emory University; Qi Long, Emory University; Aasma Shaukat, University of Minnesota; Robin E Rutherford, Emory University; Carrie R. Daniel, Emory University; Vaunita Cohen, Emory University; Chiranjeev Dash, Emory University
• Language: English
• Date: 2009-03
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2009 American Association for Cancer Research
• Final Published Version (URL): http://cancerpreventionresearch.aacrjournals.org/content/2/3/213
• Title of Journal or Parent Work: Cancer Prevention Research
• ISSN: 1940-6207
• Volume: 2
• Issue: 3
• Start Page: 213
• End Page: 223
• Grant/Funding Information: National Cancer Institute, National Institutes of Health (R01 CA104637 to R. B.); Georgia Cancer Coalition Distinguished Scholar award (to R. B.).; The National Cancer Institute and the Georgia Cancer Coalition had no influence on the design of the study; the collection, analysis, and interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript.
• Keywords: apoptosis; calcium; vitamin D; randomized controlled trial; normal colorectal mucosa
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Oncology

Abstract

Background To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop ‘treatable’ biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2×2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis in the normal colorectal mucosa. Methods Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with calcium 2.0 g/day or vitamin D3 800 IU/day, alone or in combination vs. placebo over six months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter), in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. Results After six months treatment, Bax expression along the full lengths of crypts increased 56% (p=0.02) in the vitamin D group, and 33% in both the calcium (p=0.31) and calcium plus vitamin D (p=0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; p=0.01). There were no statistically significant treatment effects on Bcl-2 expression. Conclusions Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.