The role of FGFR4 polymorphism in the development and progression of bladder cancer

Purpose Recent studies have shown that the prognosis of breast and colorectal cancer associates with an SNP (G388R) of FGFR4 gene. Due to the high frequency of the FGFR3 mutations and the potential involvement of the FGFR family in bladder cancer carcinogenesis, it is important to investigate the role that FGFR4 G388R plays in the development or progression of bladder cancer. Methods We have collected samples from 217 newly diagnosed bladder cancer patients and 155 noncancer controls. The PCR-RFLP method was used to assess the genotype of FGFR4 G388R. For the statistics analysis, we plotted the disease-free survival curve using the Kaplan-Meier method and compared the results of different groups using the log-rank test and Cox regression model. Results The analysis of the FGFR4 genotypes in the 217 patients shows an estimated 51% for Gly/Gly genotype, 41% for Gly/Arg genotype, and 8% for Arg/Arg genotype. A Similar FGFR4 G388R genotype distribution was also observed in the 155 healthy individuals (p = 0.36), suggesting that FGFR4 G388R may not be involved in the early development of bladder cancer. No clear correlation was observed between the FGFR4 G388R allele and pathological parameters such as age at diagnosis, tumor stage, and grade. Survival analysis of the patients with bladder cancer suggested that the FGFR Gly/Gly genotype might be associated with a reduced disease-free survival (median survival time = 21 months) comparing with FGFR other genotypes (median survival time = 28 months, p = 0.09) in a follow-up period over 120 months. Interestingly, homo or heterozygous carriers of FGFR4 Gly388 had a reduced disease-free survival time (p = 0.02) among patients with the tumor stage less than T3A. Conclusion Our findings suggest that the G388R FGFR4 gene may have a limited role in bladder cancer development. However, it may serve as a prognostic factor in predicting disease-free survival for patients with less than T3A stage bladder cancer and a potential target for therapeutic strategy.