TY - JOUR
T1 - A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on markers of their metabolism in normal mucosa of colorectal adenoma patients
AU - Ahearn, Thomas U.
AU - McCullough, Marjorie L.
AU - Flanders, W. Dana
AU - Long, Qi
AU - Sidelnikov, Eduard
AU - Fedirko, Veronika
AU - Daniel, Carrie R.
AU - Rutherford, Robin E.
AU - Shaukat, Aasma
AU - Bostick, Roberd M.
PY - 2011/1/15
Y1 - 2011/1/15
N2 - In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, doubleblinded, placebo-controlled 2 × 2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n = 92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P = 0.03) and CYP24A1 expression decreased 21% (P =0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P = 0.01) and CYP27B1 expression increased 159% (P = 0.06). In patients supplemented with both calcium and vitamin D 3, VDR expression increased 19% (P = 0.13) and CaR expression increased 24% (P = 0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms.
AB - In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, doubleblinded, placebo-controlled 2 × 2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n = 92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P = 0.03) and CYP24A1 expression decreased 21% (P =0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P = 0.01) and CYP27B1 expression increased 159% (P = 0.06). In patients supplemented with both calcium and vitamin D 3, VDR expression increased 19% (P = 0.13) and CaR expression increased 24% (P = 0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms.
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U2 - 10.1158/0008-5472.CAN-10-1560
DO - 10.1158/0008-5472.CAN-10-1560
M3 - Article
C2 - 21084270
AN - SCOPUS:78751551316
SN - 0008-5472
VL - 71
SP - 413
EP - 423
JO - Cancer Research
JF - Cancer Research
IS - 2
ER -