期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 19, 期 1, 页码 280-291出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-09-0448
关键词
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资金
- NIH [RO1 CA104637, R03 CA136113]
- Georgia Cancer Coalition Distinguished Scholar Award
- Franklin Foundation
- Emory Graduate School
- NATIONAL CANCER INSTITUTE [R01CA104637, R03CA136113] Funding Source: NIH RePORTER
The exact antineoplastic effects of calcium and vitamin D-3 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 x 2 factorial clinical trial to test the effects of calcium and vitamin D-3 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 D-3 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 D-3 groups, respectively, but not in the calcium plus vitamin D-3 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 D-3 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 D-3 as chemopreventive agents against colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 19(1); 280-91. (C) 2010 AACR.
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