Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial

To investigate the potential efficacy of calcium and vitamin D in reducing risk for colorectal neoplasms and to develop “treatable” phenotypic biomarkers of risk for colorectal neoplasms, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial to test the e...

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Bibliographic Details
Published in:	Cancer epidemiology, biomarkers & prevention Vol. 18; no. 11; pp. 2933 - 2941
Main Authors:	FEDIRKO, Veronika, BOSTICK, Roberd M, DANA FLANDERS, W, QI LONG, SIDELNIKOV, Eduard, SHAUKAT, Aasma, DANIEL, Carrie R, RUTHERFORD, Robin E, JOELLE WOODARD, Jill
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-11-2009
Subjects:	Adult Aged Biological and medical sciences biomarkers calcium Calcium - pharmacology cell differentiation Cell Differentiation - drug effects cell proliferation Cell Proliferation - drug effects Cholecalciferol - pharmacology clinical trial Colon - cytology Colon - metabolism colonic neoplasms Colorectal Neoplasms - prevention & control Cyclin-Dependent Kinase Inhibitor p21 - metabolism Double-Blind Method Drug Combinations Female Humans Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Male Medical sciences Middle Aged normal colorectal mucosa Pilot Projects Placebos Prognosis Telomerase - metabolism Tumors Ubiquitin-Protein Ligases - metabolism vitamin D Cell proliferation Calcium Digestive system Mucosa Gut Cell differentiation Normal Inorganic element Randomization Cancerology Vitamin D Clinical trial Colon Differentiation
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Summary:	To investigate the potential efficacy of calcium and vitamin D in reducing risk for colorectal neoplasms and to develop “treatable” phenotypic biomarkers of risk for colorectal neoplasms, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial to test the effects of these agents on cell cycle markers in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2 g/day calcium and/or 800 IU/day vitamin D 3 versus placebo over 6 months. Overall expression and distributions of p21 waf1/cip1 (marker of differentiation), MIB-1 (marker of short-term proliferation), and hTERT (marker of long-term proliferation) in colorectal crypts in the normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. In the calcium, vitamin D, and calcium plus vitamin D groups relative to the placebo, p21 expression increased by 201% ( P = 0.03), 242% ( P = 0.005), and 25% ( P = 0.47), respectively, along the full lengths of colorectal crypts after 6 months of treatment. There were no statistically significant changes in the expression of either MIB-1 or hTERT in the crypts overall; however, the proportion of hTERT, but not MIB-1, expression that extended into the upper 40% of the crypts was reduced by 15% ( P = 0.02) in the vitamin D plus calcium group relative to the placebo. These results indicate that calcium and vitamin D promote colorectal epithelial cell differentiation and may “normalize” the colorectal crypt proliferative zone in sporadic adenoma patients, and support further investigation of calcium and vitamin D as chemopreventive agents against colorectal neoplasms. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2933–41)
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-News-1 ObjectType-Feature-3 content type line 23
ISSN:	1055-9965 1538-7755
DOI:	10.1158/1055-9965.EPI-09-0239