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关于微量营养素摄入量或血液微量营养素浓度与乳腺癌风险之间的关系，已经发表的流行病学观察研究报告结果不一，而临床干预研究开展难度较大、混杂因素较多。此外，微量营养素摄入量调查主要通过问卷收集数据，客观性和准确性难以保证；血液微量营养素浓度调查又难以避免反向因果关系对研究结果的影响：究竟是微量营养素浓度影响了乳腺癌风险？还是乳腺癌风险影响了微量营养素浓度？ 2020年8月25日，国际抗癌联盟《国际癌症杂志》在线发表希腊约阿尼纳大学、世界卫生组织国际癌症研究机构、英国伦敦帝国学院、布里斯托大学的研究报告，通过孟德尔随机化，调查了根据基因预测11种微量营养素浓度与乳腺癌风险的因果关系，避免了反向因果关系以及诸多混杂因素对研究结果的影响。 该研究首先利用欧洲生物信息学研究所全基因组关联分析数据库和美国国家医学图书馆数据库，获取11种微量元素（β胡萝卜素、钙、铜、叶酸、铁、镁、磷、硒、维生素B6、维生素B12、锌）浓度全基因组关联分析数据。随后，采用逆方差加权法，对乳腺癌学会联盟12万2977例乳腺癌患者和10万5974例对照者进行孟德尔随机化分析，并进行敏感性分析以评定可能违反孟德尔随机化假设的影响。结果发现： 根据基因预测的血镁浓度每增加0.08mmol/L
根据基因预测的血磷浓度每增加0.5mg/dL
其他微量营养素与乳腺癌风险的关系不大。 根据各种敏感性分析和多重比较修正，血镁浓度与乳腺癌风险的因果关系仍然可靠。 因此，该研究结果表明，血镁和血磷浓度较高可能影响乳腺癌风险，故有必要开展进一步研究对该结果进行验证，并阐明其具体机制。 Int J Cancer. 2020 Aug 25. Online ahead of print. Genetically predicted circulating concentrations of micro-nutrients and risk of breast cancer: A Mendelian randomization study. Papadimitriou N, Dimou N, Gill D, Tzoulaki I, Murphy N, Riboli E, Lewis SJ, Martin RM, Gunter MJ, Tsilidis KK. University of Ioannina, Ioannina, Greece; International Agency for Research on Cancer, Lyon, France; Imperial College London, London, UK; University of Bristol, Bristol, UK. What's new? The epidemiological literature reports inconsistent associations between the consumption or circulating concentrations of micro-nutrients and breast cancer risk. Evidence from clinical trials is also lacking. Here, the authors conducted a Mendelian randomization study to investigate whether genetically-predicted concentrations of 11 micro-nutrients are associated with risk of breast cancer. An increased risk of overall and oestrogen-receptor positive disease was observed for genetically-predicted higher concentrations of magnesium that was robust to sensitivity analyses and correction for multiple comparisons. The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micronutrients and breast cancer risk. We investigated associations between genetically predicted concentrations of 11 micronutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, vitamin B12 and zinc) and breast cancer risk using Mendelian randomization (MR). A two-sample MR study was conducted using 122977 women with breast cancer and 105974 controls from the Breast Cancer Association Consortium. MR analyses were conducted using the inverse variance-weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions. A value of 1SD (SD: 0.08mmol/L) higher genetically predicted concentration of magnesium was associated with a 17% (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.10-1.25, P value = 9.1 × 10-7) and 20% (OR: 1.20, 95% CI: 1.08-1.34, P value = 3.2 × 10-6) higher risk of overall and ER+ve breast cancer, respectively. An inverse association was observed for a SD (0.5 mg/dL) higher genetically predicted phosphorus concentration and ER-ve breast cancer (OR: 0.84, 95% CI: 0.72-0.98, P value = .03). There was little evidence that any other nutrient was associated with breast cancer. The results for magnesium were robust under all sensitivity analyses and survived correction for multiple comparisons. Higher circulating concentrations of magnesium and potentially phosphorus may affect breast cancer risk. Further work is required to replicate these findings and investigate underlying mechanisms. KEYWORDS: breast cancer; causal inference; diet; Mendelian randomization; nutrition PMID: 32761610 DOI: 10.1002/ijc.33246
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