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Author Notes:

Requests for reprints: 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

We thank Jill Joelle Woodard and Bonita Feinstein for managing the study, Dr. Bruce W. Hollis for conducting blood vitamin D assays, Vaunita Cohen and Eileen Veronica Smith for excellent technical assistance, Christopher Farino and Stuart Myerberg for development of the study database, John Melonakos and Tauseef Rehman from DivEyes for development of the scoring software, the physicians of the Emory Clinic for work on biopsy procurement, and all study participants for their time and dedication to the study.

The National Cancer Institute, the Georgia Cancer Coalition, the Franklin Foundation, and the Emory Graduate School had no influence on the design of the study; the collection, analysis, and interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript.

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Research Funding:

National Cancer Institute, NIH grants RO1 CA104637 and R03 CA136113 and Georgia Cancer Coalition Distinguished Scholar Award (R.M. Bostick); Franklin Foundation; and Emory Graduate School supplemental research funds (V. Fedirko).

Keywords:

  • vitamin D
  • calcium
  • 8-Hydroxy-2’-deoxyguanosine
  • randomized controlled trial
  • normal colorectal mucosa
  • colonic neoplasms

Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial

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Journal Title:

Cancer Epidemiology, Biomarkers and Prevention

Volume:

Volume 19, Number 1

Publisher:

, Pages 280-291

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The exact anti-neoplastic effects of calcium and vitamin D3 in the human colon are unclear. Animal and in vitro studies demonstrated that these two agents reduce oxidative stress, but these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2×2 factorial clinical trial to test the effects of calcium and vitamin D3 on a marker of oxidative DNA damage, 8-hydroxy-2’-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (n=92) with at least one pathology-confirmed colorectal adenoma were treated with calcium 2 g/day and/or vitamin D3 800 IU/day vs. placebo over six months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After six months treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P=0.15) and 25% (P=0.10) in the calcium and vitamin D3 groups, respectively, but not in the calcium plus vitamin D3 group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor (VDR) expression (P=0.05). Overall, these preliminary results indicate that calcium and vitamin D3 may decrease oxidative DNA damage in the normal human colorectal mucosa; support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms; and provide support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms.

Copyright information:

© 2010 American Association for Cancer Research

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