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

@article{citeulike:6083188, 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. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2933-41).}, author = {Fedirko, Veronika and Bostick, Roberd M. and Flanders, W. Dana and Long, Qi and Sidelnikov, Eduard and Shaukat, Aasma and Daniel, Carrie R. and Rutherford, Robin E. and Woodard, Jill Joelle J.}, citeulike-article-id = {6083188}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1055-9965.EPI-09-0239}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19861511}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19861511}, day = {27}, doi = {10.1158/1055-9965.EPI-09-0239}, issn = {1538-7755}, journal = {Cancer epidemiology, biomarkers \& prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, keywords = {calcium, cancer, clinical, colorectal, d, trial, vitamin}, month = {October}, posted-at = {2009-11-07 18:03:52}, priority = {2}, title = {Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial.}, url = {http://dx.doi.org/10.1158/1055-9965.EPI-09-0239}, year = {2009} }

TY - JOUR ID - citeulike:6083188 L3 - citeulike-article-id:6083188 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 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. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2933-41). JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology SN - 1538-7755 TI - Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial. KW - calcium KW - cancer KW - clinical KW - colorectal KW - d KW - trial KW - vitamin AU - Fedirko, Veronika AU - Bostick, Roberd AU - Flanders, Dana AU - Long, Qi AU - Sidelnikov, Eduard AU - Shaukat, Aasma AU - Daniel, Carrie AU - Rutherford, Robin AU - Woodard, Jill Joelle PY - 2009/10/27/ UR - http://dx.doi.org/10.1158/1055-9965.EPI-09-0239 ER -