Background: CXCL12 and its receptor CXCR4 belong to the CXC family of chemokines that regulate the migration of immune cells during their development and in inflammatory responses. They also regulate the migration, proliferation and survival signals in multiple cell types, therefore deregulation of their expression or activity have been implicated in the pathogenesis, growth and metastasis of solid as well as haemato-lymphoid malignancies. A single nucleotide polymorphism (SNP) (rs1801157; G>A) have been recognized in CXCL12 gene and was linked to risk, severity and outcome of many tumors; however, its significance in NHL has not been thoroughly studied.
Aim of the study: To investigate the impact of CXCL12 (rs1801157; G>A) genetic polymorphism on risk to, clinicopathologic characteristics, response to treatment and survival in Egyptian NHL patients.
Material and methods: DNA from 80 NHL patients and 150 healthy controls were analyzed using the PCR-RFLP method for identification of the genotypes.
Results: The frequency of CXCL12 (rs1801157; G>A) GA genotype was significantly higher in NHL patients than in the control group (38.8% versus 18.7%, P=0.001) and it could be associated with increased risk of developing NHL (OR=2.8, 95% CI: 1.528-5.240).When the mutant genotypes GA and AA were considered together, they significantly associated with more frequent initial advanced clinical staging III,IV (P=0.019), IPI risk (3,4) (P=0.031), ≥2 extranodal involvement (P=0.03), higher initial serum LDH (P=0.02) when compared to GG genotype. Patients carrying the A allele (GA+AA) genotypes had significantly worse overall survival (OS) (P=0.037) and progression free survival (PFS) (P=0.047) than those with the GG genotype.
Conclusion: Our study revealed that CXCL12 (rs1801157; G>A) SNP could be considered as a risk factor for developing de novo NHL in Egyptian population and it may have a predictive and prognostic value in NHL.