IBCL-282: Genetic Polymorphisms of Death Receptor 4 (TRAIL-R1) and the Susceptibility to B-Non-Hodgkin Lymphoma among Egyptians

Context: Genetic polymorphisms of death receptor 4 (DR4), called tumor necrosis factor-related apoptosis-inducing ligand-death receptor 1 (TRAIL-R1), were involved with susceptibility to many cancers; however, there is a dearth of reports about B-non-Hodgkin lymphomas (B-NHLs), particularly from Arab-African nations. Objective: To assess the possible association between TRAIL-R1-A1322G, -C626G, and -A683C polymorphisms and B-NHL risk among Egyptians. Design: This case-control study involved 100 adult Egyptian B-NHL patients recruited from The National Cancer Institute, Cairo University. The control group consisted of 150 unrelated, age- and gender-matched healthy, Egyptian volunteers. Setting: The study is applicable in oncology clinics. Patients or other participants: B-NHL patients were diagnosed according to the WHO classification (2016). The extent of the disease was categorized according to theAnn Arbor classification, the performance status of the patients was assessed by Eastern Cooperative Oncology Group criteria, and their response to therapy was evaluated. Interventions: Genotyping of TRAIL-R1-C626G, -A683C, and -A683C was performed using PCR-based molecular assays. Main outcome measures: The highly polymorphic TRAIL-R1 gene was allied with cancer susceptibility; however, these findings are still debatable. Results: The frequency of the polymorphic alleles of -C626G and -A1322G were significantly higher in B-NHL patients compared to controls with almost two-fold increased risk of B-NHL (OR=1.76; 95% CI=1.01–3.08 and OR=2.1; 95% CI=1.61–3.74 respectively), while there was no statistical difference in the distribution of -A683C polymorphic allele between B-NHL patients and controls (OR=1; 95% CI=0.5–2). Combined genotypes analysis revealed that co-inheritance of the polymorphic genotypes of TRAIL-R1-C626G and -A1322G SNPs was associated with almost three-fold increased risk of B-NHL, while co-inheritance of the variant genotypes of -A683C and -A1322G SNPs or those of the three studied SNPs was not. Conclusions: TRAIL-R1-C626G and -A1322G polymorphisms could be considered molecular risk factors for B-NHL in Egyptian populations. 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.