Meravt Khorshied
Kasr Al Ainy School of Medicine, Cairo, Egypt
Title: Genetic variations in tumor necrosis factor related apoptosis-inducing ligand-1 and the susceptibility to B cell Non-Hodgkin lymphoma in Egypt
Biography
Biography: Meravt Khorshied
Abstract
B-cell non-Hodgkin lymphomas (B-NHL) represent a heterogeneous group of disorders characterized in most cases by genetic alterations and chromosomal translocations. As lymphoma is a multi-hit phenomenon, other genetic abnormalities including concurrent deregulation of other dominant oncogenes and/or inactivation of tumor suppressor genes (TSGs) are necessary for lymphomagenesis. Tumor necrosis factor-related apoptosis inducing ligand-1 (TRAIL1) and its receptor (TRAIL-R) engage the suicide machinery of cells and activates the apoptotic proteases to mediate apoptosis. Dysregulation of their function due to genetic alterations has been reported to play a crucial role in the pathogenesis of different cancers. To explore the possible association between TRAIL1-C626G, -A683C and -A1322G single nucleotide polymorphisms (SNPs) and the susceptibility to B-NHL in a cohort of Egyptians, we conducted a case-control study. The study included 100 B-NHL patients and 150 healthy controls. Genotyping of TRAIL1 (rs20575, rs20576, and rs2230229) SNPs was done by polymerase chain reaction technique.
Results: The frequency of polymorphic alleles of TRAIL1-C626G and A1322G SNPs was higher in B-NHL cases compared to controls and conferred twofold increased risk of B-NHL in Egyptians (OR=1.76, 95%CI=1.01-3.07 and OR=2.04, 95%CI=1.02-4.07 respectively). There was no statistical difference in the distribution of TRAIL1-A683C genotypes between B-NHL patients and controls (OR=1, 95%CI=0.5-2). Combined genotypes analysis revealed that coinheritance of TRAIL1-C626G and A1322G conferred fivefold increased the risk of B-NHL (OR=5.02, 95%CI=2.35-10.73), while coinheritance of A683C and A1322G was associated with almost threefold increased risk of B-NHL (OR=2.6, 95%CI=1/05-6.73). Co-existence of the variant genotypes of the three SNPs conferred fourfold increased risk of BNHL (OR=4.1, 95%CI=1.01-17.63). In conclusion, genetic variations in TRAIL1 gene could be considered as molecular risk factor for B-NHL among Egyptians. Deeper insight into the contribution of TRAIL1 genetic polymorphism in lymphomagenesis is recommended. Furthermore, TRAIL is a novel promising treatment target for hematological malignancies. Ultimately, functional studies concerning the role of these polymorphisms may allow the identification of potential therapeutic targets.