Abstract
Problem: There is some evidence that genetic variations at detoxifying enzymes such as glutathione S-transferase and cytochrome P450 are susceptibility factors for head and neck cancer. In multiple head and neck cancer patients an accumulation of genetic risk factors can be assumed.
Methods: Accordingly, we have examined genotype frequencies at the polymorphic gene loci GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1, and CYP2E1 and microsatellite polymorphisms at tumor necrosis factor (TNF) loci in 384 patients with single squamous cell carcinoma (SCC) of the head and neck, 39 patients with multiple SCC, and 219 controls.
Results: GSTT1 null was increased in multiple SCC patients (36.8%) compared with single SCC patients (21.2%; P = 0.014; odds ratio [OR], 2.47) and controls (22.2%; P = 0.017; OR, 2.39). GSTM3 AA was more frequent in the single SCC patients (76.6%) and multiple SCC patients (82.1%; P = 0.057; OR, 2.31) compared with controls (66.5%) but lacked significance. The TNF allele B3 was significantly increased in the single SCC group (B3-allele: 22.5%, B3/B3: 10.8%) and showed further accumulation in the multiple SCC group (B3: 30.3%, P < 0.001, OR, 2.87; B3/B3: 15.8%, P = 0.008, OR, 5.21).
Conclusion: Patients suffering from multiple SCC development showed an accumulation of high-risk genotypes at GST and TNF gene loci. We conclude that genetically encoded defects in foreign compound detoxification and immune response initiation play a role in the pathogenesis of this disease.
Significance: The identification of high-risk individuals may help to earlier diagnose second primary head and neck cancer lesions and thereby improve prognosis of the disease.
Support: None reported.