PB2071 GENETIC VARIATIONS IN TUMOR NECROSIS FACTOR‐RELATED APOPTOSIS‐INDUCING LIGAND RECEPTOR‐1 (TRAIL‐R1) GENE AND THE SUSCEPTIBILITY TO B CELL NON‐HODGKIN LYMPHOMA IN EGYPT

Background: Apoptosis is essential for normal tissue homeostasis, cellular differentiation and development. Inhibition or blockade of Tumor Necrosis Factor‐Related Apoptosis‐Inducing Ligand‐Receptor 1 (TRAIL‐R1) may alter its apoptotic function, and subsequently provide growth advantage to neoplastic cells. Genetic polymorphisms in TRAIL‐R1 gene were involved with susceptibility to many cancers, however dearth of reports about B‐non‐Hodgkin lymphomas (B‐NHLs) particularly from Arab African nations. Aims: To assess the possible association between TRAIL‐R1 ‐A1322G, ‐C626G and ‐A683 C and polymorphisms and B‐NHL risk among Egyptians. Methods Genotyping of TRAIL‐R1 ‐C626G, ‐A683 C and ‐A683 C was performed to 100 B‐NHL patients and 150 controls. Results: The frequency of polymorphic alleles of ‐A1322G and ‐C626G was higher in B‐NHL compared to controls with almost twofold increased risk of B‐NHL (OR = 2.04; 95%CI = 1.02‐4.07 and OR = 1.76; 95%CI = 1.01‐3.07 respectively), while there was no statistical difference in the distribution of ‐A683 C polymorphic allele (OR = 1; 95%CI = 0.5‐2). Combined genotypes analysis revealed that co‐existence of the three variants conferred fourfold increased risk (OR = 4.1; 95% CI = 1.01‐17.63), while co‐inheritance of ‐C626G and ‐A1322G, and co‐inheritance of ‐A683 C and ‐A1322G conferred fivefold and threefold increased the risk respectively. Summary/Conclusion: TRAIL‐R1–C626G and ‐A1322G polymorphisms could be considered as molecular risk factors for B‐NHL in Egyptian population. Furthermore, the growing interest in TRAIL‐based interventions has led to the development of recombinant human TRAIL (rhTRAIL) as a promising target therapy. Accordingly, screening for TRAIL‐R1 gene polymorphisms is mandatory for selecting patients who will gain benefit from this novel therapeutic modality