Genetic Variants in MTHFR Gene Predict ≥ 2 Radiation Pneumonitis in Esophageal Squamous Cell Carcinoma Patients Treated with Thoracic Radiotherapy.

Yang Zhang,Chengsuo Huang,Zongjuan Li,Baosheng Li,Jian Zhang,Yumei Qiao,Hongsheng Li,Qingyi Wei

doi:10.1371/journal.pone.0169147

Abstract

Reactive oxygen species (ROS), formed as an indirect production of radiotherapy (RT), could cause DNA damage of normal tissues. Meanwhile, our body possesses the ability to restore the damage by DNA repair pathways. The imbalance between the two systems could finally result in radiation injury. Therefore, in this prospective cohort study, we explored the association of genetic variants in ROS metabolism and DNA repair pathway-related genes with radiation pneumonitis (RP). A total of 265 locally advanced esophageal squamous cell carcinoma (ESCC) patients receiving RT in Chinese Han population were enrolled. Five functional single nucleotide polymorphisms (SNPs) (rs1695 in GSTP1; rs4880 in SOD2; rs3957356 in GSTA1; and rs1801131, rs1801133 in MTHFR) were genotyped using the MassArray system, and rs1801131 was found to be a predictor of ≥ 2 RP. Our results showed that, compared with TT genotype, patients with GG/GT genotypes of rs1801131 had a notably lower risk of developing ≥ 2 RP (HR = 0.339, 95% CI = 0.137–0.839, P = 0.019). Further independent studies are required to confirm this findings.

Highlights

Esophageal carcinoma was diagnosed in nearly 477,900 individuals in China alone in 2015 [1]
We examined the association between genetic variants in SOD2, GSTP1, GSTA1 and MTHFR genes and the radiation pneumonitis (RP) risk in Esophageal squamous cell carcinoma (ESCC) patients
We found that rs1801131 of MTHFR gene in the DNA repair pathway maybe a reliable and independent predictor for ! 2 RP

Summary

Introduction

Esophageal carcinoma was diagnosed in nearly 477,900 individuals in China alone in 2015 [1]. Esophageal squamous cell carcinoma (ESCC) represents approximately 95% of all cases of esophageal cancer in the Chinese population. Radiotherapy (RT), alone or in combination with chemotherapy is the mainstay for the management of locally advanced ESCC. Higher doses of RT are closely associated with improved local control; radiation pneumonitis (RP). Genetic Variants in MTHFR Gene and RP (to B.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion