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
Mené sur 92 patients présentant des adénomes colorectaux, cet essai randomisé évalue les effets chimiopréventifs d'une supplémentation en vitamine D3 et en calcium sur les processus impliqués dans la voie de signalisation APC/
Résumé en anglais
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 APC, β-catenin, and E-cadherin expression in the normal appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blinded, placebo-controlled 2x2 factorial clinical trial. Pathology-confirmed colorectal adenoma cases were treated with 2 g/day elemental calcium and/or 800 IU/day vitamin D3 versus placebo over 6 months (N=92; 23/group). Overall APC, β-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 (Φh APC) increased 21% (p=0.01), β-catenin decreased 12% (p=0.18), E-cadherin increased 72% (p=0.03), and the Φh APC/β-catenin ratio (APC/β-catenin score) increased 31% (p=0.02). In the calcium-supplemented group Φh APC increased 10% (p=0.12), β-catenin decreased 15% (p=0.08), and the APC/β-catenin score increased 41% (p=0.01). In the calcium/vitamin D3 supplemented group β-catenin decreased 11% (p=0.20), E-cadherin increased 51% (p=0.08), and the APC/β-catenin score increased 16% (p=0.26). These results support 1) that calcium and vitamin D modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms, 2) calcium and vitamin D as potential chemopreventive agents against colorectal neoplasms, and 3) the potential of APC, β-catenin, and E-cadherin expression as modifiable, pre-neoplastic risk biomarkers for colorectal neoplasms.
