The relationship between TNF-α gene promoter polymorphism (- 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer

Support Care Cancer. 2020 Feb;28(2):531-540. doi: 10.1007/s00520-019-04838-6. Epub 2019 May 10.

Abstract

Purpose: Radiotherapy (RTH) usually combined with chemotherapy (C-RTH) is the main method of treatment in head and neck cancer (HNC). The most common complication of RTH is oral mucositis (OM). At a certain stage of RTH, it occurs in almost all patients, often lead to discontinuation of treatment. Tumour necrosis factor alpha (TNF-α) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-α promoter region can potentially affect the function or expression of this cytokine, and thus modulate the risk of occurrence and intensity of OM and shortening of overall survival (OS).

Methods: The study group consisted of 62 patients with HNC in whom intensity-modulated radiation therapy (IMRT) technique was applied. The plasma TNF-α level was assessed using the ELISA Kit. Genotyping was performed using a real-time PCR method.

Results: HNC patients with the CC genotype of TNF-α (- 1211 T > C) have higher TNF-α plasma concentrations than those with T allele (10.70 vs 9.62 ng/ml). Patients with the 3rd degree of OM have significantly higher TNF-α levels after 5th (10.40 vs 9.45 ng/ml) and 7th (10.32 vs 9.60 ng/ml) week of RTH. CC genotype was related to a higher risk of 3rd degree OM development in the last weeks of RTH (5th, OR = 7.33; 7th, OR = 23.15).

Conclusions: High TNF-α plasma concentration and CC genotype of TNF-α are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-α plasma concentration and CC genotype of TNF-α are independent prognostic factors for patients subjected to RTH due to HNC.

Keywords: Head and neck cancer; Oral mucositis; Overall survival; Polymorphism; Radiotherapy; TNF-α.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Head and Neck Neoplasms / complications*
  • Head and Neck Neoplasms / diagnostic imaging*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Radiotherapy, Intensity-Modulated / methods*
  • Stomatitis / etiology*
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / adverse effects*

Substances

  • Tumor Necrosis Factor-alpha