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Author Notes:

Corresponding Author: Roberd M. Bostick, Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Northeast, Atlanta, GA 30322. Phone: 404-727-2671; Fax: 404-727-8737. rmbosti@sph.emory.edu

Subjects:

Research Funding:

National Cancer Institute : NCI

National Cancer Institute, National Institutes of Health (R01 CA104637 and R03 CA121873 to R.M.B.); Georgia Cancer Coalition Distinguished Scholar award (to R.M.B.); the Franklin Foundation.

Keywords:

  • calcium
  • vitamin D
  • colonic neoplasms
  • biomarkers
  • clinical trial

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

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Journal Title:

Cancer Research

Volume:

Volume 71, Number 2

Publisher:

, Pages 413-423

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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, double-blinded, placebo-controlled 2×2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/day elemental calcium and/or 800 IU/day vitamin D3 versus placebo over 6 months (N=92; 23/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 D3 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, pre-neoplastic risk biomarkers for colorectal neoplasms.

Copyright information:

©2010 American Association for Cancer Research

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