Skip to Content

As a result of the current Federal government funding situation, the information on this website may not be up to date or acted upon.

The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit

Updates regarding government operating status and resumption of normal operations can be found at

Discovering the causes of cancer and the means of prevention

Publications Search - Abstract View

Title: Effects of vitamin d and calcium on proliferation and differentiation in normal colon mucosa: a randomized clinical trial.
Authors: Fedirko V,  Bostick RM,  Flanders WD,  Long Q,  Sidelnikov E,  Shaukat A,  Daniel CR,  Rutherford RE,  Woodard JJ
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2009 Nov
Branches: MEB
PubMed ID: 19861511
PMC ID: PMC2784000
Abstract: 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 x 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.