A Randomized Clinical Trial of the Effects of Supplemental CalciumandVitaminD3 on theAPC/b-Catenin Pathway in the Normal Mucosa of Colorectal Adenoma Patients
نویسندگان
چکیده
APC/b-catenin pathway perturbation is a common early event in colorectal carcinogenesis and is affected by calcium and vitamin D in basic science studies. To assess the effects of calcium and vitamin D on adenomatous polyposis coli (APC), b-catenin, and E-cadherin expression in the normal appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blinded, placebocontrolled 2 2 factorial clinical trial. Pathology-confirmed colorectal adenoma cases were treated with 2 g/day elemental calciumand/or 800 IU/day vitaminD3 versus placebo over 6months (N1⁄4 92; 23/group). Overall APC, b-catenin, and E-cadherin expression and distributions in colon crypts in normal-appearing rectal mucosa biopsies were detected by standardized automated immunohistochemistry and quantified by image analysis. In the vitamin D3-supplemented group relative to placebo, the proportion of APC in the upper 40% of crypts ( h APC) increased 21% (P 1⁄4 0.01), b-catenin decreased 12% (P1⁄4 0.18), E-cadherin increased 72%(P1⁄4 0.03), and the hAPC/b-catenin ratio (APC/b-catenin score) increased 31% (P1⁄4 0.02). In the calcium-supplemented group hAPC increased 10%(P1⁄4 0.12),b-catenin decreased 15%(P1⁄4 0.08), and the APC/b-catenin score increased 41% (P 1⁄4 0.01). In the calcium/vitamin D3-supplemented group, b-catenin decreased 11% (P 1⁄4 0.20), E-cadherin increased 51% (P 1⁄4 0.08), and the APC/b-catenin score increased 16% (P1⁄4 0.26). These results support (i) that calcium and vitamin Dmodify APC, b-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms, (ii) calcium and vitamin D as potential chemopreventive agents against colorectal neoplasms, and (iii) the potential of APC, b-catenin, and E-cadherin expression as modifiable, preneoplastic risk biomarkers for colorectal neoplasms. Cancer Prev Res; 5(10); 1247–56. 2012 AACR.
منابع مشابه
A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on the APC/β-catenin pathway in the normal mucosa of colorectal adenoma patients.
APC/β-catenin pathway perturbation is a common early event in colorectal carcinogenesis and is affected by calcium and vitamin D in basic science studies. To assess the effects of calcium and vitamin D on adenomatous polyposis coli (APC), β-catenin, and E-cadherin expression in the normal appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blin...
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