Causal association of micronutrients with risk of HER2-positive and negative breast cancer: a two-way multivariate Mendelian randomization study
10.3760/cma.j.cn115807-20241016-00320
- VernacularTitle:微量元素与HER2（+/-）乳腺癌患病风险的相关性：一项双向多变量孟德尔随机化研究
- Author:
Yue LYU
1
;
Wenchao YANG
;
Zhongcheng GAO
Author Information
1. 临沂市胸科医院外科，临沂 276034
- Publication Type:Journal Article
- Keywords:
Trace elements;
Breast cancer;
Human epidermal growth factor receptor 2;
Mendelian randomization;
Vitamin B6
- From:
Chinese Journal of Endocrine Surgery
2025;19(2):187-192
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether the levels of 15 micronutrients could influence the risk of HER2-positive and negative breast cancer using Mendelian randomization (MR) .Methods:In this study, multivariate Mendelian randomization analysis was used to obtain the data of 15 micronutrients (copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, zinc, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D and vitamin E) and HER2 (+/-) breast cancer in the Genome-Wide Association Study (GWAS) database. Analyses were performed using R software and the TwoSampleMR package. This study used the inverse variance weighting (IVW) method as the main method to analyze the causal relationship between micronutrients and HER2 (+/-) breast cancer, combined with MR-Egger regression, weighted median (WM) , Simple mode, and Weighted mode as complementary methods. Heterogeneity and horizontal pleiotropy of our results were detected by the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept to enhance the reliability and stability of the results. Reverse MR analysis was performed as HER2 (+/-) breast cancer exposure factors. The micronutrients screened by the MR above analysis were used as outcome variables for effect and sensitivity analyses. Multivariate Mendelian randomization analysis was performed on the relevant trace elements screened by MR to avoid interference between variables. The independent effects of trace elements were analyzed to improve the reliability of our results.Results:The results of MR analysis showed that micronutrient vitamin B6 was negatively associated with the risk of developing HER2-negative breast cancer (IVM: OR=0.69,95% CI:0.45-0.96, P=0.029) . The results of the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept test showed that there was no heterogeneity and horizontal pleiotropy among the instrumental variables. At the same time, the analysis of leave-one-out test confirmed that a single SNP had no significant effect on the overall results, which further enhanced the reliability and stability of the results. Conclusions:Among the 15 micronutrients, our results suggested that vitamin B6 may be a protective factor for HER-negative breast cancer. Our study provided a reference for the pathogenesis of HER-negative breast cancer and its early prevention and treatment.
