PT  - JOURNAL ARTICLE
AU  - Fedirko, Veronika
AU  - Bostick, Roberd M.
AU  - Flanders, W. Dana
AU  - Long, Qi
AU  - Sidelnikov, Eduard
AU  - Shaukat, Aasma
AU  - Daniel, Carrie R.
AU  - Rutherford, Robin E.
AU  - Woodard, Jill Joelle
TI  - Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial
AID  - 10.1158/1055-9965.EPI-09-0239
DP  - 2009 Nov 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - 2933--2941
VI  - 18
IP  - 11
4099  - http://cebp.aacrjournals.org/content/18/11/2933.short
4100  - http://cebp.aacrjournals.org/content/18/11/2933.full
SO  - Cancer Epidemiol Biomarkers Prev2009 Nov 01; 18
AB  - 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 D3 versus placebo over 6 months. Overall expression and distributions of p21waf1/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)