Fibroblast Growth Factor Receptor 4 Gly388Arg Gene Polymorphism and Non-Hodgkin Lymphoma Susceptibility and Prognosis in Egyptian population: Case–control Study

Abstract

BACKGROUND: Angiogenesis is a multistep process having an essential role in the growth and progression of various tumors including hematolymphoid malignancies. Basic fibroblast growth factor (bFGF) is one of angiogenic growth factors which level is considered as prognostic factor in lymphoma and leukemia. It mediates its action by binding to high affinity cell surface receptors-fibroblast growth factor receptor 1–4 (FGFR4) with receptor kinase activity. Therefore, upregulation of BFGF-FGFR system may cause increased risk of non-Hodgkin lymphomas (NHLs). AIM: Our study aimed to determine the association between the FGFR4 Gly388Arg (rs351855G/A) polymorphism and NHL disease susceptibility and prognosis. MATERIALS AND METHODS: The present study included 75 NHL patients and 100 healthy controls. Genotyping of FGFR4 was done by Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). As after the amplification of the target gene, the PCR products were digested with BstNI restriction endonuclease enzyme. RESULTS: Analysis of FGFR4 Gly388Arg polymorphism revealed that the frequency of heterozygous (GA) mutation as well as the mutant allele (A) was significantly higher in cases compared to control subjects with p < 0.001 and 0.002, respectively. The mutant genotypes were more prevalent at older age, aggressive clinical stage, bone marrow involvement, anemia, and thrombocytopenia at presentation. The mean of overall survival and the event free survival of our NHL patients were shorter in the mutant genotypes with p = 0.049 and 0.017, respectively. CONCLUSION: This study provides evidence that FGFR4 Gly388Arg polymorphism confers a genetic susceptibility to NHL among Egyptians and has a poor prognostic impact.