Serum Iron Status and the Risk of Breast Cancer in Europeans: A 2-Sample Mendelian Randomisation Study

Abstract Background: Previous observational studies showed that there was a conflict about serum iron status and the risk of breast cancer, which could have an impact on the prevention of breast cancer.Object: We used a two sample Mendelian randomisation (MR) study to explore the causal relationship between iron status and the risk of breast cancer.Method: To select single nucleotide polymorphisms (SNPs) which could be used as instrumental variables for iron status, we used the Genetics of Iron Status consortium. Moreover, we used the OncoArray network to select SNPs of instrumental variables for the outcome (breast cancer). The conservative instruments (SNPs were all consistent with iron status) and liberal instruments (SNPs was associated with at least one of iron status) were used in MR analysis. In the conservative instruments set we used an inverse-variance weighted (IVW) approach, and in the liberal instruments set we used the IVW, MR-Egger regression, weighted median and simple mode approach. Results: In the conservative approach, none of the iron status were statistically significant for breast cancer or its subtypes. And in the liberal approach, transferrin was positively associated with ER-negative breast cancer by simple mode (OR for MR: 1.225; 95% CI: 1.064, 1.410; P=0.030). However, other iron statuses had no association with breast cancer or its subtypes (P>0.05).Conclusion: Our MR study, in the liberal approach, suggested that changes in the concentration of transferrin could increase the risk of ER-negative breast cancer, and other iron statuses had no effect on breast cancer or its subtypes. This could be verified in future studies.