Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Angiogenesis is a multistep process playing a crucial role in the growth and progression of various tumors including hematolymphoid malignancies. Studies have indicated that angiogenesis is enhanced in lymphomas. Basic fibroblast growth factor(bFGF)is importantprotein involved inangiogenesis.BFGF mediates its biological effect by binding to and activating a family of specific high-affinity cell surface receptors called fibroblast growth factor receptors (FGFR1-4) with protein tyrosine kinase activity. Therefore, up-regulation of BFGF-FGFR system may cause increased risk of non-Hodgkin lymphomas (NHLs). The present study aimed to determine an association between the FGFR4 Gly388Argpolymorphism andNHL disease susceptibility. The present study included 75 NHL patients and 100 healthy controls. Genotyping of FGFR4 was done by PCR-RFLP technique.Analysis of FGFR4 Gly388Arg polymorphism revealed similar frequencies of homozygous (AA) mutation (4%) in both patients and control subjects. The frequency of heterozygous (GA) mutation was significantly higher in cases compared to control subjects (41.3% vs 16% respectively, P value <0.001, OR = 3.780, 95% CI = 1.857- 7.698). Similarly, the mutant allele (A) frequency was significantly higher compared to control subjects(24.7%vs 12% respectively; (P value = 0.002, OR = 2.401, 95% CI= 1.364-4.227).This study provides an evidencethat FGFR4 Gly388Arg polymorphism confers geneticsusceptibilityto NHL among Egyptians and suggests an association with advanced disease.Furhermore, it suggets that NHL patients with mutant genotypes are at higher risk to have older age, bone marrow involvement, anemia and thrombocytopenia at presentation

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