Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Am J Clin Nutr. 2021 Jun 1;113(6):1490-1502. doi: 10.1093/ajcn/nqab003.
BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
背景：有关循环矿物质和维生素浓度与结直肠癌风险之间关联的文献有限且不一致。支持饮食改变或营养素补充预防结直肠癌功效的随机对照试验 (RCT) 证据也有限。
目的：为了补充观察性研究和 RCT 的发现，我们使用孟德尔随机化 (MR) 研究了 11 种微量营养素（β-胡萝卜素、钙、铜、叶酸、铁、镁、磷、硒、维生素 B-6、维生素 B-12 和锌）的遗传预测浓度与结直肠癌风险之间的关联。
方法：使用来自遗传与结直肠癌联合会、结直肠癌跨学科研究和结肠癌家族登记处的 58221 例结直肠癌患者和 67694 例对照者进行了两样本 MR。使用逆方差加权 MR 分析进行了分析，并进行了敏感性分析以评估潜在违反 MR 假设的影响。
结果：观察到遗传预测的铁浓度与结肠癌风险升高之间存在显著关联[每标准差比值比 (ORSD)：1.08；95%置信区间 (CI)：1.00，1.17；P 值=0.05]，近端结肠癌也是如此，而遗传预测的维生素 B-12 浓度与结直肠癌风险升高之间存在显著关联（ORSD：1.12；95% CI：1.03，1.21；P 值=0.01），结肠癌也是如此。遗传预测的硒浓度与结肠癌风险降低之间也存在显著关联（ORSD：0.98；95% CI：0.96，1.00；P 值=0.05），远端结肠癌也是如此。这些关联在敏感性分析中是稳健的。观察到锌与结直肠癌和远端结肠癌风险呈负相关，但无法进行敏感性分析。这些发现均未通过多重检验校正而得到保留。β-胡萝卜素、钙、铜、叶酸、镁、磷和维生素 B-6 的遗传预测浓度与疾病风险无关。
结论：这些结果表明循环铁和维生素 B-12（阳性）和硒（阴性）与结肠癌风险之间可能存在因果关联。
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