GLUTATHIONE-S-TRANSFERASE M1 AND T1 AND CYTOCHROME P4501A1 POLYMORPHISMS IN RELATION TO THE RISK FOR BENIGN AND MALIGNANT HEAD AND NECK LESIONS

BACKGROUND. Susceptibility to head and neck cancer in a particular ind ividual may depend in part on the metabolic balance between Phase 1 en zymes, such as cytochromes P450 (CYPs), and Phase II enzymes, such as glutathione S-transferases (GSTs). Genetic variability in CYP and GST isoenzymes may contribute to individual differences in susceptibility to chemical carcinogenesis. GSTM1 and GSTT1 null genotypes as well as polymorphic variants in the CYP1A1 gene that may help determine the ri sk for head and neck cancer have been described in previous reports. M ETHODS. Polymorphisms of GSTM1, GSTT1, and CYP1A1 in whole blood were detected by polymerase chain reaction (PCR) in 185 patients with head and neck squamous cell carcinoma (HNSCC), 78 patients with benign head and neck lesions (BHNL), and 207 blood donors. RESULTS. GSTM1 null ge notype was demonstrated to be equally frequent in patients with HNSCC (50.8%), patients with BHNL (47.4%), and blood donors (51.7%). GSTT1 n ull genotype occurred significantly more often in patients with BHNL ( 33.3%) as compared with blood donors (20.3%), demonstrating that lack of GSTT1 may be a risk factor for BHNL. Presence of the rare valine in the CYP1A1/Nco1 site was found in 33 patients with HNSCC (17.8%), in 20 patients with BHNL (25.6%), and in 34 blood donors (16.4%). The fre quencies with which the presence of the rare cytosine nucleotide in th e CYP1A1/Msp1 site was detected were 17.8%, 15.4%, and 15.9%, respecti vely. CONCLUSIONS. The occurrence of polymorphic variants in the GSTM1 , GSTT1, and CYP1A1 genes did not differ between the groups investigat ed, therefore indicating no significant contribution to the developmen t of head and neck cancer. (C) 1998 American Cancer Society.