GLUTATHIONE AND GLUTATHIONE S-TRANSFERASES IN HUMAN SQUAMOUS-CELL CARCINOMAS OF THE LARYNX AND GSTM1 DEPENDENT RISK

Background: The aim of the present study was to establish the risk of squamous cell carcinoma (SCC) of the larynx associated with the congen ital absence of glutathione S-transferase MI (GSTMl), and to describe the expression of the isoenzymes GSTA1/2, GSTPl-1, and GSTMl and gluta thione (GSH) content in healthy and tumoral larynx tissue. Material an d Methods: Blood samples fr om 160 SCC male patients and 158 controls were phenotyped for GSTMl by ELISA. Using 37 paired samples (normal an d tumour specimens) fram cancer patients we carried out a descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH) Res ults: GSTMl null phenotype was more common in the SCC group than in co ntrols (OR 1.9, Cls 1.18-3.05, p=0.004). Total GST activity was higher in tumour samples than in matched healthy tissue (2.2-fold, p-0.00001 ), being largely determined by GSTPl-1 (1.9-fold ina eased in malignan t tissue; p=0.0003). The GSH content was also significantly higher in SCC than in normal mucosa (1.9-fold, p=0.0007). Conclusions: We confir med the GSTMl-dependent risk for larynx cancer among smokers. The over expression of the GST/GSH system in tumours reported here indicates th eir possible role in chemoresistance to pharmacological therapy.