Influence of polymorphisms at glutathione-S-transferase gene loci on allelic losses in head and neck squamous cell carcinomas.

Background: While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk. Material and methods: We examined genotype frequencies from leukocyte DNA of 269 laryngeal 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 chromosomal gene loci were determined in 37 of the study patients by comparing blood and tumor cell DNA. The relationship between high risk genotypes and the occurrence of LOH was investigated. Results: Glutathione-5-transferase high risk genotypes were identified at the first and third 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 statistically significant influence on the occurrence of LOH in the tumor tissue. Conclusion: There is evidence that the polymorphisms studied play a role in the carcinogenic process by influencing the chromosomal fragility which may lead to the inactivation of tumor suppressor genes or the activation of oncogenes.