Genetic variations in tumor necrosis factor related apoptosis-inducing ligand receptor-1 (TRAIL-R1) gene and the susceptibility to b-cell non-hodgkin lymphoma (B-NHL) in Egypt1

Abstract

BACKGROUND: Dysregulated apoptosis is a hallmark of cancer development and progression. TRAIL and its receptors (R1 and R2) are key players in the extrinsic apoptotic pathway. Genetic alteration or blockade of TRAIL-R1 may alter its apoptotic function, and subsequently provide growth advantage to neoplastic cells. OBJECTIVE: to investigate the possible association between -C626G, -A683C and -A1322G single nucleotide polymorphisms (SNPs) of TRAIL-R1 gene and the susceptibility to B-NHL in a cohort of Egyptians. METHODS: Genotypic analysis was performed for 100 newly diagnosed B-NHL patients and 150 age and gender matched healthy controls. RESULTS: The polymorphic alleles of -C626G and -A1322G conferred almost twofold increased risk of B-NHL (OR = 1.76; 95%CI = 1.01–3.22 and OR = 1.89; 95%CI = 1.01–3.75 respectively). There was no statistical difference in the distribution of TRAIL-R1-A683C alleles/genotypes between B-NHL patients and controls. B-NHL risk increased when -C626G and -A1322G polymorphic genotypes were co-inherited (OR = 3.57; 95%CI = 1.29–9.84). The risk conferred by -C626G SNP increased for DLBCL (OR = 3.39, 95% CI: 1.61–7.16). CONCLUSION: TRAIL-R1–C626G and -A1322G polymorphisms could be considered as molecular risk factors for B-NHL especially DLBCL. The data provided by the current study constitute an initial millstone towards developing a large-scale dataset for genetic variations that could contribute to lymphomagenesis in Egyptian population.