Glutathione S-transferase and cytochrome-P-450 polymorphism as risk factors for squamous cell carcinoma of the larynx.

PURPOSE

While cigarette smoking and alcohol consumption are recognized covariates for laryngeal carcinoma, the role of genetic factors in determining individual susceptibility is unknown. We describe the influence of polymorphism in carcinogen-metabolizing enzymes on susceptibility to squamous cell carcinoma of the larynx.

MATERIAL AND METHODS

We investigated 269 patients with T1-T4 laryngeal carcinoma and 216 controls. Enzyme genotypes at the glutathione-S-transferase GSTM1 (A, B, A/B, null), GSTM3 (A, B), GSTT1 (null and expressors), and cytochrome P-450, CYP2D6 (intron 3/exon 4 boundary mutation and exon 5 deletion), CYP1A1 (3'-mutation and exon 7 mutation), and CYP2E1 (mutation at the 5' flanking region) loci were determined using polymerase chain reaction and restriction-based approaches.

RESULTS

While the frequencies of the heterozygote GSTM1 A/B and homocygote GSTM3 B/ B were statistically significantly lower in cases than controls, the frequency of the GSTT1 null genotype was higher in the cases than controls. Genotype frequencies of 123 patients suffering squamous cell carcinomas located at different sites within the upper aerodigestive tract showed no differences between cases and controls.

CONCLUSIONS

The data provide evidence that susceptibility to laryngeal carcinoma, but not pharyngeal carcinoma, is mediated by allelism at a number of loci encoding enzymes involved in the detoxification of electrophils derived from environmental pollution including cigarette smoke.