The role of MYD88 and CXCR4 gene polymorphisms in the etiopathogenesis, clinical parameters and prognosis in hodgkin lymphoma and non-hodgkin lymphoma patients

Background and aim: Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) are common hematopoietic malignancies with hundreds of thousands of new diagnoses each year worldwide. Although many factors play a role in the development of these diseases, environmental factors and genetic factors are known to be highly effective. In recent years, mutations carried by MYD88 and CXCR4 genes have been implicated in many solid organ and hematologic malignancies and these studies are of great importance for new treatment approaches. The aim of this study was to evaluate the role of MYD88 and CXCR4 gene polymorphisms in etiopathogenesis and response to treatment in Hodgkin's and Non-hodgkin's lymphoma patients and to determine the relationship with clinical parameters. Methods: The study included 70 patients diagnosed with Hodgkin's lymphoma and treated and followed up in Gaziantep University, Şahinbey Training and Research Hospital and 70 patients diagnosed with Non-Hodgkin's lymphoma and treated and followed up in Gaziantep University, Şahinbey Training and Research Hospital. DNA isolation was performed from peripheral blood obtained from these patients. Genotyping was performed using Real-time PCR and Sequence analysis (Sanger Sequence) method for CXCR4 gene 2228014-rs SNP mutation and MYD88-L265P SNP mutation in the genomic DNAs obtained. Results: CXCR4 rs2228014 SNP mutation was found to be 13 (18,5%) TT mutant and 57 (81,5%) CC alele in HL patients and 11 (15,7%) TT mutant and 59 (84,3%) CC wild type alele in NHL patients. There is a statistically significant association between these diseases and SNP (p<0.05). MYD88 L265P SNP mutation was found to be 3 (4,2%) CC mutant and 67 (95,8%) TT wild type allele in HL patients and 5 (7,1%) CC and 65 (92,9%) TT allele in NHL patients. There was no statistically significant association between these diseases and SNP (p<0.05). In conclusion, there is a statistically significant association between CXCR4 rs2228014 SNP mutation in HL and NHL patients (p<0.05). There is a statistically significant association between MYD88 L265P SNP mutation in HL and NHL patients (p<0.05). A significant difference was found between MYD88 L265P mutant CC allele (χ²=11.748, p<0.001) and CXCR4 (χ²=28.475, p<0.001) mutant TT allele genes and progression status in NHL patients. However, the risk of progression is high for both genes. A significant difference was observed between the MYD88 L265P mutant CC allele (χ²=9.055, p=0.015) and CXCR4 mutant TT allele (χ²=10.736, p=0.003) genes and progression status in HL patients. MYDX88 and CXCR4 mutant group had a higher risk of progression than the wild type group. Conclusion; Our study shows that the frequency of MYD88 L265P and CXCR4 rs2228014 mutations in HL and NHL patients can be used to predict clinical outcome and may play a role in lymphoma pathogenesis. In addition, genetic studies are very important in determining the prognosis of patients. In our study, it was also concluded that bone marrow involvement among clinical parameters can be used as an independent risk factor in determining prognosis. Further genetic analyses such as whole genome analysis and prospective studies with more patients are required to confirm our findings.