Association of the prognostic role of FGFR4 Gly388Arg polymorphism with treatment outcomes after chemoradiotherapy in esophageal cancer.

Abstract

60 Background: Fibroblast growth factor receptor 4 (FGFR4) has been associated with increased risk, staging, and metastasis in several type of cancer. The purpose of this study was to evaluate the prognostic role of FGFR4 Gly388Arg polymorphism in esophageal cancer after chemoradiotherapy. Methods: Peripheral blood samples from 250 patients who were treated with chemoradiotherapy were used for this study. Patients were diagnosed as a stage of I in 12 (5%), II in 54 (21%), III in 115 (46%) and IV in 69 (28) patients. All of the patients were received chemotherapy using cisplatin and fluorouracil or docetaxel. Results: The overall response was 85%, with 21% complete response and 64% partial response. The overall survival (stage II, 34months; stage III, 23.3 months; stage IV, 19.3 months, p=0.005) and progression survival (stage II, 23.8 months; stage III, 12.8 months; stage IV, 9 months, p=0.001) was significantly improved according to stage. In FGFR4 genotypic analysis, 96 patients (38.6%) were homozygous for Gly388 allele, with 113 heterozygous (45.4%) and 40 (16.0) homozygous for Arg388 allele. There was no significant association between FGFR4 genotype and stage. However, Gly388 allele patients show better overall response rate (90.6%) than Arg388 carriers (82.4%, p=0.050). In early stage (I, II, n=66), Gly388 allele patients tendted to have a better OS (p=0.898) or PFS (p=0.597) than Arg388 carriers. However, in advanced stage (III, IV), the survival outcomes was similar between genotypes. Conclusions: Present study shows that FGFR4 Gly388 allele has a prognostic role in response after chemoradiotherapy in esophageal cancer. Especially in early stage of esophageal cancer, FGFR4 might have an important role in disease progression and survival outcomes. It suggests that the possibility of new therapeutic target for esophageal cancer treatment.