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 M1 (GSTM1), and to describe the expression of the isoenzymes GSTA1/2, GSTP1-1, and GSTM1 and glutathione (GSH) content in healthy and tumoral larynx tissue.

MATERIAL AND METHODS

Blood samples from 160 SCC male patients and 158 controls were phenotyped for GSTM1 by ELISA. Using 37 paired samples (normal and tumour specimens) from cancer patients we carried out a descriptive study of enzyme activity by ELISA (GSTs) and Ellman's as say (GSH) RESULTS: GSTM1 null phenotype was more common in the SCC group than in controls (OR 1.9, CIs 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 GSTP1-1 (1.9-fold increased 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 GSTM1-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.