Serum iron status and the risk of breast cancer in the European population: a two-sample Mendelian randomisation study

Genes & Nutrition

Qunying Wu¹  Huifeng Wang¹  Chenyang Hou²  Tingxi Lu²  Yuang Mao²  Qingzhi Hou³  Yanling Hu⁴  Xing Xie⁴  Yongcong Liang⁴  Yueliang Chen⁴ 

[1] Department of Biochemistry and Molecular Biology, School of Pre-Clinical Medicine, Guangxi Medical University, 530000, Nanning, Guangxi, China;Department of Information and Management, Guangxi Medical University, 530000, Nanning, Guangxi, China;Department of Occupational Health and Environmental Health, School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), 271000, Taian, Shandong, China;Life Sciences Institute, Guangxi Medical University, 530000, Nanning, Guangxi, China;

关键词: Iron status;    Breast cancer;    ER-positive breast cancer;    ER-negative breast cancer;    Mendelian randomisation;   

DOI  :  10.1186/s12263-021-00691-7

来源: Springer

【 摘 要 】

BackgroundPrevious 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.ObjectWe used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer.MethodTo 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.ResultsWhen 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).ConclusionIn 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.

【 授权许可】

CC BY