Smoking and alcohol abuse cause squamous cell carcinoma of the head and neck (SCCHN) through smoke-induced mutations, which are counteracted by O(6)-methylguanine-DNA methyltransferase (MGMT). This study aimed at elucidating the role of MGMT in SCCHN and its precursor lesions (SIN). MGMT was also determined in the normal mucosa (NM) and blood lymphocytes (PBLCs).
Results: a) MGMT was lower in NM than in PBLCs. b) Smoking reduced MGMT in NM but had no effect in PBLCs. c) MGMT activity increased in the sequence NM<SIN II and III<CIS. d) There was no correlation between MGMT and prognostic parameters or clinical course in SCCHN. The data suggest that MGMT becomes down-regulated due to smoking in non-cancerous pharyngeal mucosa. The low MGMT activity in early dysplastic mucosal lesions may increase the risk for tumour development. Since some advanced carcinomas showed low MGMT activity, chemotherapy with O(6)-alkylating agents might be an alternative option.