Abstract 842: Differences in supplemental calcium and vitamin D3 treatment effects on potential biomarkers of risk for colorectal neoplasms according to calcium receptor and vitamin D receptor expression

Abstract

Abstract Background: Evidence suggests that calcium and vitamin D have anti-neoplastic effects in the colorectal mucosa; and that many of these effects are modulated by the calcium receptor (CaR) and vitamin D receptor (VDR); however, this has not been investigated in humans. To evaluate differences of effects of calcium and vitamin D according to CaR and VDR expression, we conducted a secondary analysis of data from a clinical trial of the effects of supplemental calcium and vitamin D3 on biomarkers of risk for colorectal adenomas. 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. A panel of potential biomarkers of risk in colon crypts was detected in biopsies of normal-appearing colorectal mucosa using standardized automated immunohistochemistry and novel image analysis methods. Participants were stratified based on the median treatment effects on CaR and VDR expression in the study population. Treatment effects relative to the placebo group were calculated using a MIXED effects model as implemented in SAS v9.2. Results: Relative to the placebo group, those in the calcium treatment (calcium) group who had greater than the median increases in CaR expression (CaR high), had greater mean increases in p21, TGFβ1, and MSH2 expression than those with a lower than the median increase in CaR expression (CaR low). Among those in the vitamin D3 treatment (D3) group who were CaR high, there were greater mean increases in E-cadherin, APC, p21, TGFβ1, and MSH2 expression, and greater mean decreases of the Bax/Bcl2 expression ratio than in those who were CaR low. Among those in the calcium + vitamin D3 (Ca+D3) treatment group who were CaR high, there were greater mean increases in TGFβ1 and MSH2 expression than in those who were CaR low. Relative to the placebo group, those in the calcium group who had greater than the median increases in VDR expression (VDR high), had greater mean increases in APC, p21, TGFβ1, MLH1, and MSH2 expression, and a greater mean decrease in the Bax/Bcl2 expression ratio than were seen in those with a lower than the median increase in VDR expression (VDR low). Among those in the D3 group who were VDR high, there were greater mean increases in E-cadherin, APC, p21, TGFβ1, and MSH2 expression than in those who were VDR low. Among those in the Ca+D3 group who were VDR high, there were greater increases in APC, p21, MLH1, and MSH2 expression than in those who were VDR low. Discussion: These preliminary results suggest that anti-neoplastic effects of calcium and vitamin D3, individually or in combination on the normal colorectal mucosa may depend on CaR and VDR expression, and provide additional support for CaR and VDR as modifiable biomarkers of risk for colorectal neoplasms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 842. doi:10.1158/1538-7445.AM2011-842