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Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial
Open accessAbstract
The exact antineoplastic effects of calcium and vitamin D3 in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, 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 2 g/d calcium and/or 800 IU/d vitamin D3 versus placebo over 6 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 6 months of 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 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. Cancer Epidemiol Biomarkers Prev; 19(1); 280–91
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“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [150]
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“Treatment with vitamin D has been shown to decrease 8—hydroxy–2—deoxyguanosin, a marker of endogenous oxidative damage to DNA [150], increase Bax, a protein coding gene involved in apoptosis [150], regulates poly-ADP-ribose polymerase activity in the DNA damage response pathway [151], stabilize chromosomal structure and prevent double strand breaks [152].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [150]
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Metadata
- Authors
- Fedirko, V., Bostick, R. M., Long, Q., Flanders, W. D., McCullough, M. L., Sidelnikov, E., Daniel, C. R., Rutherford, R. E., & Shaukat, A.
- Affiliations
- American Cancer Society (US)
- Corresponding author
- Bostick, Roberd M.
- ORCID
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2010-01-01
- Volume
- 19
- Issue
- 1
- Pages
- 280-291
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC2805163
- OpenAlex
- W2112110686
- Cited by
- 150
- References
- 59
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 2 · 2021: 8 · 2020: 12 · 2019: 6 · 2018: 13 · 2017: 2 · 2016: 9 · 2015: 13 · 2014: 15 · 2013: 15 · 2012: 17
- FWCI
- 10.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgia Cancer Coalition
- Emory University
- National Institutes of Health
- National Cancer Institute (R03CA136113, R01CA104637)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- vitamin D3, calcium supplementation, oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, colorectal mucosa, vitamin D receptor, colorectal adenoma, colorectal cancer chemoprevention, oxidative stress, DNA damage biomarkers
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Adenoma, Adult, Aged, Calcium Carbonate, Calcium, Dietary, Cholecalciferol, Deoxyguanosine, DNA Damage, Double-Blind Method, Female, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Intestinal Mucosa, Intestinal Neoplasms, Male, Middle Aged, Pilot Projects, Precancerous Conditions, Biomarkers, Tumor, Oxidative Stress, Dietary Supplements
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