Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women's Health Initiative randomized trial
Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: Reanalysis of Women's Health Initiative randomized trial
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DOI：
10.1002/ijc.23311
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发表时间：
2008-04-15
影响因子：
6.4
通讯作者：
Giovannucci, Edward L.
中科院分区：
文献类型：
--
作者：
Ding, Eric L.;Mehta, Saurabh;Giovannucci, Edward L.
尽管钙和维生素D的摄入量在几个大型前瞻性研究中一直被证明与结直肠癌风险呈负相关，并在多个随机试验中被证明是预防腺瘤和癌症的，但妇女健康倡议(WHI)的钙和低剂量维生素D补充试验没有发现对结直肠癌的总体影响。然而，先前的报告没有认识到雌激素治疗的重要生物相互作用。我们通过重新分析WHI钙和维生素D补充试验(1,000毫克元素钙、400IU维生素D3或安慰剂)的主要数据结果，重新分析了同时随机接受雌激素干预和安慰剂的妇女的结果，研究了雌激素与钙和维生素D对结直肠癌风险的治疗相互作用。结果表明，同期雌激素治疗是钙和维生素D补充剂对结直肠癌风险的强烈影响修饰物。在同时接受雌激素治疗的女性中，补充钙和维生素D表明风险增加(危险比=1.5，95%CI：0.962.33)，而在同时被分配到雌激素试验的安慰剂组的女性中，补充钙和维生素D显示了暗示的益处(HR=0.71，95%CI：0.46-1.09)(p-for-雌激素交互作用=0.018)。报道的雌激素使用也发现了一致的交互作用(p交互作用=0.037)。结果表明，同时接受雌激素治疗的钙和维生素D对结直肠癌风险的影响是不同的。尽管有必要进行进一步的临床和机制研究，但应该认识到雌激素治疗与钙和维生素D补充剂之间明显相互作用的潜在临床意义。讨论了与关键的膜受体megalin和雌激素依赖蛋白calbindin相关的重要生物学机制。(C)2007年Wiley-Liss，Inc.
Although calcium and vitamin-D intake were consistently shown to be inversely associated with colorectal cancer risk in several large prospective studies and protective against adenoma and cancer in multiple randomized trials, the Women's Health Initiative (WHI) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer. However, the previous report did not recognize an important biologic interaction with estrogen therapy. We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a reanalysis of primary data results from the WHI calcium and vitamin-D supplementation trial (1,000 mg elemental calcium, 400 IU of vitamin-D3, or placebo), reanalyzing results from women concurrently randomized to estrogen interventions and placebo. Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk. While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk (Hazard Ratio = 1.50, 95% CI: 0.96-2.33), among women concurrently assigned to placebos arms of the estrogen trials, calcium plus vitamin-D indicated suggestive benefits (HR = 0.71, 95% CI: 0.46-1.09) (p-for-estrogen-interaction = 0.018). Consistent interaction was also found by reported estrogen use (p interaction = 0.037). Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk. Although further clinical and mechanistic studies are warranted, the potential clinical implications of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized. Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed. (c) 2007 Wiley-Liss, Inc.