Abstract 2890: Effects of calcium and vitamin D on markers of vitamin D metabolism in normal colon mucosa: A randomized clinical trial

Abstract

Abstract Background: In colon cancer cell lines and rodent models calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis and affect and are affected by local expression of the vitamin D receptor (VDR), CYP27B1, and CYP24A1; however, the latter has not been investigated in humans. To evaluate the effects of supplemental calcium and vitamin D3 on VDR, CYP27B1, and CYP24A1 expression in the normal colorectal epithelium, we conducted a randomized, double-blinded, placebo-controlled 2×2 factorial clinical trial. Methods: Ninety-two men and women with at least one pathology-confirmed sporadic colorectal adenoma were treated with calcium 2 g/day or vitamin D3 800 IU/day, alone or in combination vs. placebo over six months. VDR, CYP27B1, and CYP24A1 were detected in biopsies of normal-appearing colorectal mucosa using standardized automated immunohistochemistry, and their overall expression and distributions within the colon crypts were quantified by novel image analysis methods. The relative treatment effects were calculated and assessed using a MIXED effects model as implemented by SAS v9.2. Results: Relative to the placebo group, in the calcium + vitamin D3 group VDR expression increased 19% (p=0.13) along the full length of crypts, 19% (p=0.09) in the upper 40% (differentiation zone) of crypts, and 31 % (p=0.13) in the lower 60% (proliferation zone) of crypts. In the vitamin D3 only group CYP27B1 expression increased 259% (p=0.04) along the full length of crypts, 211% (p=0.04) in the upper 40% of crypts, and 210% (p=0.04) in the lower 60% of crypts. CYP24A1 expression along the full length of crypts decreased 21% (p=0.51) in the calcium group, and increased 65% (p=0.22) and 51% (p=0.37) in the vitamin D3 and calcium + vitamin D3 groups, respectively. Discussion: These preliminary results 1) suggest that, as hypothesized, calcium and vitamin D3, individually or in combination may modulate VDR, CYP27B1, and CYP24A1 expression in the normal-appearing human colorectal epithelium, which may promote normal patterns of cell proliferation, differentiation, and apoptosis; 2) provide further evidence to the potential importance of vitamin D metabolism and its autocrine/paracrine function in colorectal mucosa; 3) provide support for the efficacy of calcium and vitamin D3 in reducing risk for colorectal neoplasms; and 4) present the potential of the VDR and CYP27B1 and CYP24A1 as potential modifiable biomarkers of risk for colorectal neoplasms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2890.