The GNAS1 T393C Polymorphism Predicts Survival in Patients With Advanced Squamous Cell Carcinoma of the Larynx

Abstract

In previous studies, we have demonstrated that the T-allele of a specific single nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with increased Galphas expression and hence apoptosis. The T-allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro- and hypopharynx. The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens. DNA analysis was performed using DNA from paraffin-embedded tissue samples from 157 patients (142 men, 15 women) with a median follow-up of 68 (3-143) months. The various genotypes were correlated with the overall survival. Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III-IV) with an apparent gene-dose effect (P = .0437). Five-year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01-6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals. The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.