The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is associated with breast cancer subtype susceptibility in southwestern China

Zhen Li; Ji Zhang; Wei Zou; Qi Xu; Siyuan Li; Jie Wu; Li Zhu; Yunjiao Zhang; Lei Xu; Ying Zhang; Qingsong Luo; Jianyun Nie; Xingxu Li; Tianning Zou; Ceshi Chen

doi:10.1371/journal.pone.0254267

The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is associated with breast cancer subtype susceptibility in southwestern China

PLoS One. 2021 Jul 9;16(7):e0254267. doi: 10.1371/journal.pone.0254267. eCollection 2021.

Authors

Zhen Li¹, Ji Zhang¹, Wei Zou², Qi Xu³, Siyuan Li⁴, Jie Wu⁵, Li Zhu⁵, Yunjiao Zhang⁶, Lei Xu⁵, Ying Zhang¹, Qingsong Luo¹, Jianyun Nie¹, Xingxu Li⁵, Tianning Zou¹, Ceshi Chen^{4

7}

Affiliations

¹ Department of Breast Surgery, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
² Queen Mary Institute, Nanchang University, Nanchang, China.
³ Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas, Austin, Texas, United States of America.
⁴ Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
⁵ Yunnan Economy & Society Bigdata Research Institute, Yunnan University of Finance and Economics, Kunming, Yunan, China.
⁶ Kunming Medical University Haiyuan College, Kunming, Yunnan, China.
⁷ China Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.

Abstract

Methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme, is reportedly involved in several cancer types. The MTHFR C677T polymorphism influences many biological processes, including tumorigenesis. However, the association between the MTHFR C677T polymorphism and breast cancer (BC) subtypes is not fully understood. In this study, the MTHFR C677T polymorphism was genotyped in 490 individuals with or without BC from southwestern China. Analysis of the association between the MTHFR C677T polymorphism and BC revealed that there was a significant association between the MTHFR C677T polymorphism and triple-negative breast cancer (TNBC) (OR = 2.83, 95% CI: 1.12-9.51, P = 0.0401). Furthermore, the MTHFR C677T polymorphism can also serve as a protective factor in luminal A breast cancer (OR = 0.57, 95% CI: 0.34-0.94, P = 0.0258). Evaluation of the association between the MTHFR C677T polymorphism and clinical characteristics indicated that people who suffered from hypertension had an increased risk for BC (OR = 2.27; 95% CI: 1.08-4.6; P = 0.0264), especially TNBC (OR = 215.38; 95% CI: 2.45-84430.3; P = 0.0317). Our results suggest that the MTHFR C677T polymorphism is significantly associated with susceptibility to luminal B breast cancer and TNBC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics*
China
Female
Genetic Predisposition to Disease
Humans
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Middle Aged
Polymorphism, Single Nucleotide

Substances

MTHFR protein, human
Methylenetetrahydrofolate Reductase (NADPH2)

Grants and funding

This research work has been supported by the National Nature Science Foundation of China (grant 82060481,81830087, U1602221 and 31771516); the National Key R&D Program of China (grant 2018YFC2000400); the Science and Technology Innovation Team of Yunnan Province (grant 2018HC002 and 2019HC005); the Science and Technology Program of Yunnan Province [grant 2019FE001(-309)]; the Research Institutions attached to the Health and Family Planning Commission of Yunnan Province (grant 2017NS180). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Siyuan Li employed by (Group) Co., Ltd. did play a role in our study for part of statistical analysis.