TY - JOUR
T1 - Effects of vitamin D and calcium on proliferation and differentiation in normal colon mucosa
T2 - A randomized clinical trial
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
PY - 2009/11
Y1 - 2009/11
N2 - 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. Ninetytwo men and women with at least one pathologyconfirmed 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 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 v itamin 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.
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. Ninetytwo men and women with at least one pathologyconfirmed 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 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 v itamin 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.
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U2 - 10.1158/1055-9965.EPI-09-0239
DO - 10.1158/1055-9965.EPI-09-0239
M3 - Article
C2 - 19861511
AN - SCOPUS:72749118086
SN - 1055-9965
VL - 18
SP - 2933
EP - 2941
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 11
ER -