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Glutathione-associated enzymes in head and neck squamous cell carcinoma and response to cisplatin-based neoadjuvant

A Cabelguenne1, M A Loriot, I Stucker

  • 1Laboratoire de Toxicologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM U490), Paris, France.

International Journal of Cancer
|July 31, 2001
PubMed

Insights

Genetic variations in glutathione S-transferases (GSTs) are linked to increased laryngeal cancer risk. Lower plasmatic GSTP1 levels correlate with better chemotherapy response in head and neck squamous cell carcinoma patients.

Area of Science:

  • Biochemistry
  • Oncology
  • Genetics

Background:

  • Glutathione S-transferases (GSTs) are crucial phase II metabolic enzymes involved in detoxifying reactive compounds.
  • GSTs play a significant role in xenobiotic metabolism, detoxification, and have been implicated in carcinogenesis, particularly epithelial transformations.
  • Genetic polymorphisms in GSTs (GSTM1, GSTT1, GSTP1) exist and influence their function and clinical outcomes.

Purpose of the Study:

  • To investigate the role of GST enzymes (GSTP1, GSTM1, GSTT1) in the development of head and neck squamous cell carcinoma (HNSCC).
  • To explore the association between GST alterations, p53 mutation status, and clinical response to chemotherapy in HNSCC patients.
  • To identify potential predictive biomarkers for chemotherapy response in HNSCC.

Main Methods:

  • Prospective study of a large cohort of HNSCC patients.
  • Analysis of genetic polymorphisms in GSTM1, GSTT1, and GSTP1.
  • Correlation analysis between GST genotypes, p53 mutation status, and chemotherapy response.
  • Measurement of plasmatic GSTP1 levels and multivariate analysis.

Main Results:

  • Increased risk of laryngeal cancer associated with GSTM1 null genotype (2.6-fold) and homozygous GSTP1 val105 genotype (2.8-fold).
  • Homozygous GSTP1 val105 genotype was over-represented in the p53 mutation group (p=0.05).
  • Significantly lower plasmatic GSTP1 levels observed in complete responders compared to partial and non-responders (p=0.05).
  • Higher prevalence of p53-mutated tumors in non-responders (81%) compared to responders (p=0.05).
  • Multivariate analysis identified p53 mutations and high tumor stage as independent factors for non-response, while plasmatic GSTP1 levels and low tumor stage predicted complete response.

Conclusions:

  • GST enzymes are associated with larynx cancer development.
  • GST genetic polymorphisms and plasmatic GSTP1 levels may serve as predictive factors for chemotherapy response in HNSCC.
  • Further exploration of GST enzymes as predictive factors and therapeutic targets in HNSCC is warranted.

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