The association between HLA-E gene and genetic susceptibility of nasopharyngeal carcinogenesis

Abstract

Nasopharyngeal carcinoma (NPC) is a geographically restricted tumor. The tumor is rare in the western world but more prevatent in Southern China and many Asian countries including Thailand. The etiologic factors identified for NPC include environmental and genetic factors. Emigrant Chinese individuals in several countries showed a higher incidence of NPC than the indigenous individuals suggested that the genetic of host play a major role for NPC development. Previous studies reported the association between NPC and HLA (human leukocyte antigen) such as HLA-A2 and HLA-B46, which present antigen to T lymphocyte that is important in viral infection and tumor. However, the explanation of this association is still unclear. Latter studies suggested that the NPC susceptibility genes are not the HLA-A or HLA-B genes, but may be other genes within the HLA region, near the D6S1624 microsatellite locus. In our study, we are interested in HLA-E, which is in close proximity to D6S1624 microsatellite locus and plays important role in NK and CTL - mediated lysis. This study was conducted to compare SNP of the HLA-E gene between NPC patients and normal controls of the same ethnic origins; Thai, Chinese and Thai-Chinese. Seven positions of SNPs in HLA-E region were determined by PCR-SSOP in 174 patients with NPC and 200 healthy blood donors. As the results, only two SNPs (codon 77 and 107) show polymorphism. While changes in codon 77 is a silent mutation. codon 107 polymorphism leads to a missense muatation changing arginine to glycine. Analysis of SNP pattern at codon 107 shows a significant association between HLA-E107G allele and NPC patients of Thai origin with OR (95% CI), 1.78 (1.16-2.74), p=0.006. The effect of HLA-E107G was similar to that of an autosomal recessive gene, in which two homozygous alleles, but not heterozygous, were required to increase the relative risk, OR (95% CI), 2.11 (1.15-3.88), p=0.009. In addtion, haplotype analysis of two HLA-E SNPs, 77C/T and 107A/G has confirmed the role of HLA-E107G for NPC development. In conclusion, HLA-E107G allele might be important in the nasopharyngeal carcinogenesis of the Thai population, possibly via inhibition of NK cell or CTL function against EBV infected-tumor cell.