Association of GSTP1 and ERCC1 polymorphisms with toxicity in locally advanced head and neck cancer platinum-based chemoradiotherapy treatment

Head Neck. 2019 Aug;41(8):2704-2715. doi: 10.1002/hed.25754. Epub 2019 Apr 11.

Abstract

Background: Platinum-based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous-cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity.

Methods: Thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes were genotyped in 110 patients treated with cisplatin-based CRT. DNA was obtained from blood samples, and SNP analysis was performed using a MassARRAY iPLEX Gold (Sequenom) method.

Results: Patients with ERCC1 rs11615-C allele (P = .0066), ERCC1 rs735482-C allele (P = .0204), and ERCC4 rs1799801-C allele (P = .0286) had lower risk of grade 2-3 hematologic toxicity. In addition, the presence of G allele of GSTP1 was associated with a significantly lower risk of severe dysphagia (P = .0004).

Conclusion: Polymorphisms in ERCC1 and GSTP1 may act as prognostic factors of acute toxicity during treatment with CRT in HNSCC patients.

Keywords: candidate gene; chemoradiotherapy; head and neck; polymorphism; toxicity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Chemoradiotherapy / adverse effects*
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / therapy
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Prospective Studies
  • Risk Factors

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin