ERCC1 C8092A polymorphism predicts fair survival outcome in Japanese patients with pharyngo-laryngeal squamous cell carcinoma

Eur Arch Otorhinolaryngol. 2020 Feb;277(2):601-610. doi: 10.1007/s00405-019-05731-y. Epub 2019 Nov 20.

Abstract

Purpose: To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC).

Methods: A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors.

Results: Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; p = 0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery.

Conclusion: The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.

Keywords: DNA repair; Head and neck cancer; Japanese; Single nucleotide polymorphism; Survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genotype
  • Humans
  • Japan
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / mortality
  • Male
  • Middle Aged
  • Pharyngeal Neoplasms / genetics*
  • Pharyngeal Neoplasms / mortality
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • X-ray Repair Cross Complementing Protein 1 / genetics*

Substances

  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • ERCC1 protein, human
  • Endonucleases