Objective: Association of glutathione-S-transferase M1 (GSTM1) polymorphisms and cancer has been demonstrated. Possible underlying mechanisms and genotype-phenotype correlations are not adequately investigated. The aim of this study was to investigate the influence of the GSTM1-null-genotype on the level of GSTM enzyme concentration and on the enzyme activity of GST in patients with head and neck cancer (HNC).
Methods: We investigated in 83 patients and 91 healthy controls the GSTM1 polymorphisms, GSTM1 protein concentration, GSTM1 protein in tumor tissues, and total GST enzyme activity.
Results: Total GST enzyme activity was significantly lower in patients with HNC (208 +/- 9 micromol/min*l) than in controls (264 +/- 11 micromol/min*l, P< 0.0001) but did not depend on GSTM1-genotype (P = 0.1). GSTM protein concentration in null-genotype patients (3.6 +/- 2.5 microg/mL, mean +/- SE) was significantly lower than in GSTM1 allele carriers (26.7 +/- 9.6 microg/ml, P< 0.0001); GSTM protein expression did not depend on GSTM1-genotype (P> 0.5).
Conclusion: GST enzyme activity in patients with HNC is suppressed, indicating impaired detoxification capacity of tobacco-smoke-related carcinogens. This suppression is not correlated with the GSTM1-genotype.