Abstract 1167: The GNAS1 T393C polymorphism is a predictor of clinical outcome in esophageal cancer

Abstract

Abstract Background: There is a paucity of prognostic markers in esophageal cancer (EC). Genetic variations determined in the germline DNA of cancer patients may serve as important prognostic factors of clinical outcome since genomic DNA remains unbiased by instability occurring in tumor DNA and is easily accessible in the peripheral blood. G-protein α subunit (Gαs) polymorphism has been identified as a prognostic marker of tumor recurrence and survival in various tumor entities. We genotyped the single nucleotide T393C polymorphism in the GNAS1 gene encoding Gαs, and focused on three different genotypes, TT, TC, and CC. The aim of this study was to evaluate the potential prognostic value of the GNAS1 polymorphism in EC. Methods: Genomic DNA was extracted from peripheral blood leucocytes of 190 patients who underwent complete resection for esophageal cancer and did not receive any neoadjuvant or adjuvant therapy. The GNAS1 genotypes were correlated with clinicopathological parameters, tumor cell dissemination in bone marrow and clinical outcome. Results: The TT and TC genotypes correlated with advanced disease, predominantly characterized by the presence of lymph node metastases (p<0.001) and tumor cell dissemination (p=0.01). In line with this, significantly more TT and TC genotype patients displayed disseminated tumor cells in bone marrow compared to the CC genotype group (p=0.01). Accordingly, the disease recurrence rate was higher in TT and TC than in CC patients. Kaplan-Meier estimates for disease-free (DFS) and overall survival (OS) displayed better outcome in CC compared to TT and TC genotypes. Furthermore, in multivariate Cox proportional hazard analysis, GNAS1 polymorphism independently predicted disease progression with the CC group presenting the best outcome (OS: p=0.001, DFS p=0.002). Conclusion: The GNAS1 polymorphism was identified as a strong independent prognostic factor for DFS and OS in EC patients supporting a functional role of Gαs in this tumor entity. Preoperative determination of the GNAS1 polymorphism will allow allocation of patients into different risk profiles as well as stratification into individual therapy regimen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1167.