Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients

Onco Targets Ther. 2016 Sep 9:9:5603-9. doi: 10.2147/OTT.S104890. eCollection 2016.

Abstract

Purpose: The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms.

Patients and methods: Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor-node-metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model.

Results: Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21-79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515-12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047-10.125; P=0.041).

Conclusion: MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer.

Keywords: MTHFR; breast cancer; methylenetetrahydrofolate reductase; recurrence risk; rs9651118 polymorphism.