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

PLoS One. 2017 Jan 3;12(1):e0169147. doi: 10.1371/journal.pone.0169147. eCollection 2017.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / radiotherapy*
  • China
  • DNA Repair
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / radiotherapy*
  • Female
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Radiation Pneumonitis / etiology
  • Radiation Pneumonitis / genetics*
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Reactive Oxygen Species
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Grants and funding

This work was supported by National Nature Science Foundation of China, grant No. 81530060, and Taishan Scholars Program of Shandong Province, China, grant No. Ts20120505 (to B.L.). This work was also supported by Shandong Province Natural Science Foundation ZR2012HL33 (H.L.) and ZR2013HL049 (to C.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.