Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.
Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.
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DOI：
10.1158/1055-9965.epi-09-0448
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Shaukat A
中科院分区：
文献类型：
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作者：
Fedirko V;Bostick RM;Long Q;Flanders WD;McCullough ML;Sidelnikov E;Daniel CR;Rutherford RE;Shaukat A
钙和维生素D3在人类结肠中的确切抗肿瘤作用尚不清楚。动物和体外研究表明，这两种药物可以降低氧化应激，但这些发现从未在人类中进行过研究。为了解决这个问题，我们进行了一项先导性、随机、双盲、安慰剂对照、2×2析因临床试验，以测试钙和维生素D3对正常结直肠粘膜中氧化DNA损伤标志物8-羟基-2 '-脱氧鸟苷（8-OH-dG）的影响。患有至少一种病理学证实的结直肠腺瘤的患者（n=92）接受钙2 g/天和/或维生素D3 800 IU/天与安慰剂治疗6个月。通过标准化自动免疫组化检测正常直肠粘膜活检组织中8-OH-dG的总体标记和结肠直肠隐窝分布，并通过图像分析进行定量。治疗6个月后，钙和维生素D3组沿着结肠直肠隐窝全长的8-OH-dG标记分别下降了22%（P=0.15）和25%（P=0.10），但钙+维生素D3组没有下降。在基线结肠隐窝维生素D受体（VDR）表达较高的参与者中，估计的治疗效果最强（P=0.05）。总体而言，这些初步结果表明，钙和维生素D3可以减少正常人结直肠粘膜中的氧化DNA损伤;支持结肠直肠隐窝中的8-OH-dG标记是结直肠肿瘤风险的可治疗的氧化DNA损伤生物标志物的假设;并为进一步研究钙和维生素D3作为结直肠肿瘤的化学预防剂提供支持。
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.