ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1560776
Association of folate metabolism-related enzymes (MTHFR, MYD88, and TP53) and their single nucleotide polymorphisms with breast cancer susceptibility in women from Southwest China: A Bayesian network approach
Provisionally accepted
- 1Yunnan College of Finance and Economics, Kunming, Yunnan, 650106, China
- 2Yunnan University of Finance and Economics, Kunming, Yunnan, 650221, China
- 3Yunnan Key Laboratory of Breast Cancer Precision Medicine, Second Department of Breast Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, 650118, China
- 4Department of Breast Surgery, Third People's Hospital of Honghe Prefecture, Cancer Hospital of Honghe Prefecture, Honghe 661400, China
- 5Kunming Medical University Haiyuan College, Kunming 650106, China
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Background: Breast cancer remains one of the most prevalent malignant tumors affecting women globally. Genetic factors are significant contributors to its pathogenesis. Single nucleotide polymorphisms (SNPs), as a common form of genetic variation, have garnered considerable attention in recent years. However, most studies have predominantly focused on associations between individual loci and breast cancer susceptibility, while the complex interactions among multiple loci across different genes remain insufficiently explored. Methods:To analyze high-dimensional multi-locus variables, chi-square test and random forests were employed. Bayesian networks, a sophisticated statistical model, were used to investigate SNP interactions across multiple genes and to construct a comprehensive genetic susceptibility model for female breast cancer. Results:The study analyzed 980 samples, comprising 490 breast cancer patients and 490 controls. Key intergenic genotypes were identified involving SNPs in TP53 (rs1042522), MTHFR (rs1801133), MTHFR (rs56221660), MTRR (rs1801394), MTR-A2756G (rs1805087), MYD88 (rs7744), and rs7851696. These interactions were associated with a significant increase in breast cancer prevalence, rising from 48.2% in the original data to 99% under the largest posterior probability combination. External validation further demonstrated a breast cancer prevalence of 70%, underscoring the robustness of the model. Conclusions: Interactions among the TP53, MYD88, and folate metabolism-related genes (MTHFR, MTR, and MTRR) may play a critical role in breast cancer susceptibility.
Keywords: breast cancer, SNPs (Single nucleotide polymorphism), Bayesian Networks (BNs), Folate(folic acid), MyD88, TP53
Received: 14 Jan 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Li, Gong, Zhao, Kong, Liu, Liu, Zhang and Zhen. 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: Li Zhen, Yunnan Key Laboratory of Breast Cancer Precision Medicine, Second Department of Breast Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, Yunnan, 650118, China
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