GLUTATHIONE-S-TRANSFERASE AND CYTOCHROME-P450 GENOTYPES AS RISK-FACTORS FOR LARYNGEAL CARCINOMA

While cigarette smoking and alcohol consumption have been linked to la ryngeal squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. We describe the role of allelism at the glutathione S-transferase GSTM1, GSTM3, GSTT1 and cytochrome P450 CYP1A1, CYP2E1, CYP2D6 loci in determining individual susceptibility to laryngeal SCC. Enzyme genotypes were determined usin g polymerase chain reaction and restriction enzyme digestion of leukoc yte DNA collected from 269 patients with T1-T4 laryngeal carcinomas an d 216 controls. While the frequencies of the heterozygote GSTM1 A/B ge notype and the homozygote GSTM3 B/B genotype were statistically signif icantly lower in the patients with tumors than in controls, the freque ncy of the GSTT1 null genotype was higher in the patients than in cont rols. The data suggest that allelism at GST loci mediates susceptibili ty to SCC of the larynx. GSTM1 A/B and GSTM3 B/B appear to be associat ed with reduced risk, while GSTT1 null may confer increased risk. Thes e findings are compatible with the view that genetic predisposition is important in determining risk for this cancer.