Genetic variants in NKG2D axis and susceptibility to Epstein –Barr virus-induced nasopharyngeal carcinoma

AbstractBackgroundNasopharyngeal carcinoma (NPC) is a rare epithelial carcinoma arising from the nasopharyngeal region. The pathogenesis of NPC is linked to Epstein –Barr virus (EBV) infection, although genetics and lifestyle factors appears to be also implicated. NKG2D is an immunoreceptor expressed by NK and T-cell subsets that recognizes MICA protein and other ligands on tumor cells. NKG2D interaction with MICA plays a role in the immunosurveillance to vir uses and cancer.MethodsWe investigated potential associations between functional polymorphisms inNKG2D andMICA genes with NPC susceptibility. We conducted a case –control study including 255 Vietnamese patients with EBV + non-differentiated NPC and 220 healthy controls.ResultsWe observed a significant association between the LNK/LNK genotype of rs1049174 (a variant associated with lower NKG2D receptor expression and reduced NK cell cytotoxicity) and increased susceptibility to NPC (adjusted OR  = 1.66, 95% CI 1.07–2.59;p = 0.024). Similarly, the AA genotype ofMICA rs2596542 was significantly associated with NPC (adjusted OR  = 2.12; 95% CI 1.22–3.81;p = 0.009). In addition, tumor specimens of NPC patients with the AA genotype displayed a higher expression level of MICA proteins and showed higher EBV titers compared with tumor tissues from patients with the GG or GA genotypes. Higher EBV copy numbers were also observed in tumors with the A al lele ofMICA rs1051792 (also known as MICA-129 Met/Va...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research