Genetic variants in NKG2D axis and susceptibility to Epstein-Barr virus-induced nasopharyngeal carcinoma.
BACKGROUND
Nasopharyngeal 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 viruses and cancer.


METHODS
We investigated potential associations between functional polymorphisms in NKG2D and MICA genes with NPC susceptibility. We conducted a case-control study including 255 Vietnamese patients with EBV + non-differentiated NPC and 220 healthy controls.


RESULTS
We 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 of MICA 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 allele of MICA rs1051792 (also known as MICA-129 Met/Val) compared with those with the G allele; however, MICA rs1051792 variants were not associated with NPC susceptibility. These results suggest that genetic variants in components of the NKG2D axis may influence the individual susceptibility to EBV-induced NPC.
['Viet|Nguyen Hoang|NH|', 'Trung|Nguyen Quang|NQ|', 'Dong|Le Thanh|LT|', 'Trung|Ly Quoc|LQ|', 'Espinoza|J Luis|JL|http://orcid.org/0000-0002-1794-6666']
D000328:Adult D016022:Case-Control Studies D004279:DNA, Viral D020031:Epstein-Barr Virus Infections D005260:Female D020022:Genetic Predisposition to Disease D014644:Genetic Variation D004854:Herpesvirus 4, Human D015395:Histocompatibility Antigens Class I D006801:Humans D007150:Immunohistochemistry D007694:Killer Cells, Natural D008297:Male D008875:Middle Aged D055655:NK Cell Lectin-Like Receptor Subfamily K D000077274:Nasopharyngeal Carcinoma D009303:Nasopharyngeal Neoplasms D020641:Polymorphism, Single Nucleotide
Nasopharyngeal carcinoma NKG2D receptor Epstein–Barr virus Head and neck neoplasms Single-nucleotide polymorphism