INFLUENCE OF POLYMORPHISMS AT GLUTATHIONE -S-TRANSFERASE GENE LOCI ONALLELIC LOSSES IN HEAD AND NECK SQUAMOUS-CELL CARCINOMAS

Background: While cigarette smoking and chronic alcohol consumption ar e the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk. Material and me thods: We examined genotype frequencies from leukocyte DNA of 269 lary ngeal cancer patients, 123 pharyngeal cancer patients and 216 controls . Polymorphisms at different glutathione-5-transferase (GST) gene loci were investigated. Losses of heterozygosity (LOH) at 12 different chr omosomal gene loci were determined in 37 of the study patients by comp aring blood and tumor cell DNA. The relationship between high risk gen otypes and the occurrence of LOH was investigated. Results: Glutathion e-5-transferase high risk genotypes were identified at the first and t hird genes of the M family (GSTM1, GSTM3) and the first gene of the P family (GSTP1). These high risk genotypes are seen to have a statistic ally significant influence on the occurrence of LOH in the tumor tissu e. Conclusion: There is evidence that the polymorphisms studied play a role in the carcinogenic process by influencing the chromosomal fragi lity which may lead to the inactivation of tumor suppressor genes or t he activation of oncogenes.