Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma

We have investigated the association between the polymorphisms of drug-meta bolizing enzymes and susceptibility to head-and-neck squamous-cell carcinom a (HNSCC). PCR-based analysis was performed on 145 Japanese patients and 16 4 healthy Japanese controls to determine genotypes of polymorphisms in CYP1 A1, CYP2E1, GSTM1 , GSTP1, and NAT2. Patients and controls were compared by multivariate analysis. The CYP1A1 Val/Val genotype was seen more frequentl y in patients than in controls [odds ratio (OR) 4.1, p = 0.038). The freque ncy of the slow plus intermediate NAT2 genotypes was also higher in patient s (OR 2.0, p = 0.039). When we analyzed the distributions of the genotypes in 69 laryngeal and 45 pharyngeal cancer patients, laryngeal cancer patient s had a higher frequency of NAT2 slow or intermediate genotype (OR 2.7, p = 0.011) and GSTP1 AA genotype (OR 2.4, p = 0.047) than controls. Pharyngeal cancer patients had a higher frequency of the CYP1A1 Val/Val genotype than controls (OR 5.7, p = 0.034), suggesting that different organs may be resp onsive to different chemicals from the environment. Furthermore, 23 patient s who developed multiple cancers (HNSCC plus other) were compared with 115 patients with HNSCC alone. There was no significant difference in the polym orphisms between the 2 groups, though excessive alcohol consumption (more t han 50 g/day of ethanol) appeared to be a risk factor for multiple cancers (p = 0.053). Int. J. Cancer 80:685-688, 1999, (C) 1999 Wiley-Liss, Inc.