Previous observational studies have provided conflicting results on the association between serum iron status and the risk of breast cancer. Considering the relevance of this relationship to breast cancer prevention, its elucidation is warranted. We used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer. To select single nucleotide polymorphisms (SNPs) that could be used as instrumental variables for iron status, we used the Genetics of Iron Status consortium, which includes 11 discovery and 8 replication cohorts, encompassing 48,972 individuals of European descent. Moreover, we used the OncoArray network to select SNPs that could be considered instrumental variables for the outcome of interest (breast cancer); this dataset included 122,977 individuals of European descent with breast cancer and 105,974 peers without breast cancer. Both conservative (SNPs associated with overall iron status markers) and liberal (SNPs associated with the levels of at least one iron status marker) approaches were used as part of the MR analysis. For the former, we used an inverse-variance weighted (IVW) method, whereas for the latter, we used the IVW, MR-Egger regression, weighted median and simple mode methods. When the conservative approach was used, iron status showed no significant association with the risk of breast cancer or any of its subtypes. However, when the liberal approach was used, transferrin levels were found to be positively associated with the risk of ER-negative breast cancer based on the simple mode method (OR for MR, 1.225; 95% CI, 1.064, 1.410; P = 0.030). Nevertheless, the levels of the other iron status markers showed no association with the risk of breast cancer or its subtypes (P > 0.05). In our MR study, the liberal approach suggested that changes in the concentration of transferrin could increase the risk of ER-negative breast cancer, although the levels of other iron status markers had no effect on the risk of breast cancer or its subtypes. This should be verified in future studies.

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欧洲人群中血清铁状态和患乳腺癌的风险：一项两样本孟德尔随机化研究

先前的观察性研究在血清铁状态与乳腺癌风险之间的关联方面提供了相互矛盾的结果。考虑到这种关系与乳腺癌预防的相关性，有必要对其进行阐明。我们使用两样本孟德尔随机化 (MR) 研究来探索血清铁状态与乳腺癌风险之间的因果关系。为了选择可用作铁状态工具变量的单核苷酸多态性 (SNP)，我们使用了铁状态遗传学联盟，其中包括 11 个发现队列和 8 个复制队列，包括 48,972 名欧洲血统的个体。此外，我们使用 OncoArray 网络选择可以被视为感兴趣结果（乳腺癌）的工具变量的 SNP；该数据集包括 122，977 名欧洲血统患有乳腺癌，105,974 名同龄人没有患乳腺癌。保守（与总体铁状态标记相关的 SNP）和自由（与至少一种铁状态标记的水平相关的 SNP）方法都用作 MR 分析的一部分。对于前者，我们使用了逆方差加权 (IVW) 方法，而对于后者，我们使用了 IVW、MR-Egger 回归、加权中值和简单模式方法。当使用保守方法时，铁状态与乳腺癌或其任何亚型的风险没有显着关联。然而，当使用自由方法时，发现转铁蛋白水平与基于简单模式方法的 ER 阴性乳腺癌风险呈正相关（MR 的 OR，1.225；95% CI，1.064、1.410；P = 0.030 ）。尽管如此，其他铁状态标志物的水平与乳腺癌或其亚型的风险无关（P > 0.05）。在我们的 MR 研究中，宽松的方法表明，转铁蛋白浓度的变化可能会增加 ER 阴性乳腺癌的风险，尽管其他铁状态标志物的水平对乳腺癌或其亚型的风险没有影响。这应该在未来的研究中得到验证。