Immunohistochemical and molecular genetic studies of the influence of glutathione-S-transferase as risk factors for the development of head and neck carcinomas.

Background: While cigarette smoking and alcohol consumption are the major risk factors for the development of head and neck carcinomas, it is assumed that genetic factors contribute to risk. The aim of this study was to characterize the influence of the carcinogen metabolizing glutathione-S-transferases on susceptibility to head and neck carcinomas. Patients and methods: Polymorphisms at GSTM1, M3, T1 and P1 gene loci were determined in 398 head and neck cancer patients and 216 controls using polymerase chain reaction and restriction enzyme digestion. The epithelial distribution of the GSTs was determined by immunohistochemical methods. Results: The GSTM1 A/B genotype was less frequent in all tumor groups compared with controls. The GSTM3 B/B genotype was reduced only in the laryngeal cancer group whereas GSTP1 A/A showed significant differences between pharyngeal cancer patients and controls. Accordingly, GSTM3 was expressed only in the cilia of the laryngeal respiratory epithelium. In contrast, GSTP1 was distributed throughout all outer layers of the squamous cell epithelium. Conclusions: While GSTM1 seems to influence susceptibility to all head and neck cancers, GSTM3 and P1reflected site-specific differences. Thus GSTM3 appears to be associated with altered risk only to laryngeal cancer whereas GSTP1 is likely to influence pharyngeal cancer risk.