Chenyang Hou1, Qingzhi Hou2, Xing Xie3, Huifeng Wang4, Yueliang Chen3, Tingxi Lu1, Qunying Wu4, Yongcong Liang3, Yanling Hu5, Yuang Mao6. 1. Department of Information and Management, Guangxi Medical University, Nanning, 530000, Guangxi, China. 2. Department of Occupational Health and Environmental Health, School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, 271000, Shandong, China. 3. Life Sciences Institute, Guangxi Medical University, Nanning, 530000, Guangxi, China. 4. Department of Biochemistry and Molecular Biology, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning, 530000, Guangxi, China. 5. Life Sciences Institute, Guangxi Medical University, Nanning, 530000, Guangxi, China. ylhupost@163.com. 6. Department of Information and Management, Guangxi Medical University, Nanning, 530000, Guangxi, China. maoyuang@gxmu.edu.cn.
Abstract
BACKGROUND: 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. OBJECT: We used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer. METHOD: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: 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. OBJECT: We used a two-sample Mendelian randomisation (MR) study to explore the causal relationship between serum iron status and the risk of breast cancer. METHOD: 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. RESULTS: 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). CONCLUSION: 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.
Entities:
Keywords:
Breast cancer; ER-negative breast cancer; ER-positive breast cancer; Iron status; Mendelian randomisation
Authors: Daniel A Quintana Pacheco; Disorn Sookthai; Mirja E Graf; Ruth Schübel; Theron Johnson; Verena A Katzke; Rudolf Kaaks; Tilman Kühn Journal: Int J Cancer Date: 2018-04-01 Impact factor: 7.396
Authors: Anjali Gaur; Helen Collins; Wahyu Wulaningsih; Lars Holmberg; Hans Garmo; Niklas Hammar; Göran Walldius; Ingmar Jungner; Mieke Van Hemelrijck Journal: Cancer Causes Control Date: 2013-05-07 Impact factor: 2.506