Prognostic significance of genetic variants in GLUT1 in stage III non-small cell lung cancer treated with radiotherapy

Thorac Cancer. 2021 Mar;12(6):874-879. doi: 10.1111/1759-7714.13851. Epub 2021 Jan 31.

Abstract

Background: To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non-small cell lung cancer (NSCLC) who received radiotherapy.

Methods: Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression-free survival (PFS) was analyzed.

Results: Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39-0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47-0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22-0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31-0.85, p = 0.009) compared to those with other diplotypes.

Conclusions: These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.

Keywords: GLUT1; non-small cell lung cancer; polymorphisms; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Female
  • Genetic Variation
  • Glucose Transporter Type 1 / genetics*
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis

Substances

  • Glucose Transporter Type 1
  • SLC2A1 protein, human