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 congenital absence of glutathione S-transferase MI (GSTMl), and to describe the expression of the isoenzymes GSTA1/2, GSTPl-1, and GSTMl and glutathione (GSH) content in healthy and tumoral larynx tissue. Material and Methods: Blood samples fr om 160 SCC male patients and 158 controls were phenotyped for GSTMl by ELISA. Using 37 paired samples (normal and tumour specimens) fram cancer patients we carried out a descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH) Results: GSTMl null phenotype was more common in the SCC group than in controls (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 malignant 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 confirmed the GSTMl-dependent risk for larynx cancer among smokers. The overexpression of the GST/GSH system in tumours reported here indicates their possible role in chemoresistance to pharmacological therapy.