GTSP1 expression in non-smoker and non-drinker patients with squamous cell carcinoma of the head and neck

PLoS One. 2017 Aug 17;12(8):e0182600. doi: 10.1371/journal.pone.0182600. eCollection 2017.

Abstract

Introduction: The main risk factors for head and neck squamous cell carcinoma (HNSCC) are tobacco and alcohol consumption and human papillomavirus (HPV) infection. However, in a subset of patients, no risk factors can be identified. Glutathione S-transferase π (GTSP1) is a carcinogen-detoxifying enzyme that is activated by exposure to carcinogens, and it is associated with a reduction in response to toxic therapies. We studied the expression of GTSP1 in tumor and non-tumor tissue samples from patients with and without these risks to identify whether GTSP1 expression differs according to exposure to carcinogens.

Materials and methods: Non-smoker/non-drinker (NSND) and smoker/drinker (SD) patients were matched according to age, gender, tumor site, TNM stage, grade and histological variants to establish 47 pairs of patients who have been previously tested for HPV. GTSP1 immunostaining was analyzed using a semi-quantitative method with scores ranging from 0 to 3 according to the area of immunostaining.

Results: GTSP1 expression was detected in the tumors of both groups. GTSP1 expression was higher in the non-tumor margins of SD patients (p = 0.004). There was no association between GTSP1 expression and positivity for HPV. No differences in survival were observed according to GTSP1 staining in tumors and non-tumor margins.

Conclusion: This study showed that GTSP1 was expressed in tumors of HNSCC patients regardless of smoking, drinking or HPV infection status. The difference in GTSP1 expression in non-tumor margins between the two groups may have been due to two possible reasons. First, elevated GTSP1 expression in SD patients might be the result of activation of GTSP1 in response to exposure to carcinogens. Second, alternatively, impairment in the detoxifying system of GTSP1, as observed by the reduced expression of GTSP1, might make patients susceptible to carcinogens other than tobacco and alcohol, which may be the underlying mechanism of carcinogenesis in the absence of risk factors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / epidemiology*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Female
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism
  • Head and Neck Neoplasms / epidemiology
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Male
  • Middle Aged
  • Papillomavirus Infections / epidemiology*
  • Smoking / epidemiology*

Substances

  • Glutathione Transferase

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Grant number 04/12054-9, http://www.fapesp.br/; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, no grant number, Research scholarship to Pamela de Oliveira Soares, http://www.capes.gov.br. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.