ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1599724
Genetic prediction of the casual relationship between micronutrients and ER+ breast cancer: a Mendelian randomized study
Provisionally accepted
- 1Department of Thyroid and Breast Surgery, Ningbo First Hospital, Ningbo, China
- 2The First Affiliated Hospital of Ningbo University, Ningbo, China
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Background: Estrogen receptor-positive (ER+) breast cancer, a prevalent subtype of breast malignancy, demonstrates complex etiological associations with multiple risk factors. Micronutrients, as essential nutritional components for human physiology, may potentially influence the pathogenesis and progression of breast carcinoma. This investigation employs Mendelian randomization (MR) methodology to assess causal relationships between 15 micronutrients and ER+ breast cancer. Methods: In this study, instrumental variables (IVs) for 15 micronutrients were extracted from the genome-wide association studies (GWAS) database, including copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E, and zinc. Concurrently, summary data related to ER+ breast cancer were obtained from the FinnGen database. Following the selection of appropriate IVs, we conducted a two-sample MR analysis. This analytical framework incorporated comprehensive sensitivity analyses to evaluate potential heterogeneity and horizontal pleiotropy, with the inverse variance weighted (IVW) method established as the principal analytical approach. Results: The findings of our study revealed a significant causal relationship between vitamin B6 and ER+ breast cancer. Notably, genetically predicted elevated vitamin B6 levels were significantly associated with an increased risk of ER+ breast cancer [Odds Ratio (OR): 1.275; 95%Confidence Interval (CI): (1.017-1.600); P = 0.035]. In contrast, no statistically significant associations were observed between the other 14 micronutrients and ER+ breast cancer risk (P > 0.05 for all). Conclusion: Our results indicated that higher concentrations of vitamin B6 may be positively associated with ER+ breast cancer risk, and further research is needed to elucidate the underlying biological mechanisms of this association. This study provides new insights into understanding the role of micronutrients in breast cancer.
Keywords: micronutrient, estrogen receptor-positive breast cancer, Vitamin B6, Mendelian randomization, risk factor
Received: 25 Mar 2025; Accepted: 16 Jul 2025.
Copyright: © 2025 Fu, Wang, Luo, Wei, Dai and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hehe Wang, The First Affiliated Hospital of Ningbo University, Ningbo, China
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