Genetic predisposition for the development of head and neck carcinoma

While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that gen etic factors contribute to risk. Glutathione-S-transferase GSTM1 AB, GSTM3 BE and GSTP1 AA as well as TNF genotypes were determined from leucocyte DNA in 392 patients with head and neck carcinoma and 216 controls, with added immunohistochemical studies. Comparative genomic hybridization was used to screen for genetic alterations in the tumor tissue. Results: White the freq uency of GSTM1 AB was significantly lower in all head and neck carcinomas c ompared with controls, GSTM3 BE was significantly lower in the laryngeal an d GSTP1 AA in the oral cavity/pharyngeal carcinoma cases; the frequency of the TNFb3 allele was higher in the laryngeal cases. Chromosomal alterations were specific for head and neck carcinomas, differing both in well differe ntiated and undifferentiated and in metastasizing and non-metastasizing tum ors. Conclusions: Allelism at GST gene loci mediates susceptibility to head and neck carcinomas: GSTM1 AB is associated with a lower risk for all head and neck carcinomas, GSTM3 BE only for laryngeal carcinomas and GSTP1 AA o nly for oral cavity/pharyngeal carcinomas. The TNFb3 allele was significant ly more frequent in laryngeal cancer patients. The genetic alterations in t he tumor tissue are in line with the "tumor progression model". Genetic con ditions are important from the first exposure with carcinogens up to late g enetic events in the tumor tissue.