Table 4. Genetic risk for NPC: HLA and immune responses to Epstein-Barr virus (EBV).

Gene/function	Study
Human leukocyte antigen (HLA)	Linkage analysis studies in Hong Kong and Singapore show HLA association with NPC[18]
	HLA-A2-B46 haplotype is associated with NPC in Taiwan[16]
	RFLP study in Tunisia shows HLA-G (facilitates escape from cancer immunosurveillance); Ile 110 allele is less frequent among patients with lymph node involvement and more severe tumor stage, and deletion of C in codon 130 was associated with decreased NPC-free disease and survival[132]
T-cell receptor (TCR) and Toll-like receptor (TLR) in EBV infection and immune response	PCR-RFLP analysis of TCR gene in Singaporean study shows TCR polymorphism is associated with decreased NPC risk, particularly in patients with HLA B46[133]
	PCR and direct sequencing of TLR polymorphism in Guangzhou study shows TLR3 polymorphism is related to NPC susceptibility but the effect is modest[134]
	TLR4 SNP may modulate immune response to EBV and predispose to NPC[135]
Host cell immune response to EBV	Microarray profiling of tumor and normal. EBV latent genes were confirmed to strongly associate with suppression of MHC class I HLA gene[4]
	DC-SIGN promoter SNP analysis in a Cantonese population shows two SNPs on DC-SIGN promoter are associated with high risk for NPC[136]
	CTLA-4 polymorphism analysis in a Hangzhou study shows that CTLA-4 SNP is highly associated with NPC susceptibility[137]
	TNFα and HSP70-2 polymorphisms in a Tunisian study show the HSP70-2 genotype is associated with increased NPC risk[138]
	PCR-RFLP analysis in a Taiwan study shows that p21WAF/CIP1 and TNFα polymorphisms have no association with NPC; comparison between smokers and non-smokers shows the association of environmental factor with the p21 in NPC[139]
	TNFα polymorphism in Portuguese study shows NPC risk increased in undifferentiated NPC[140]
Miscellaneous	Genotyping in a Guangzhou study shows an association of EBV-positive serology and genetic factors represented by tag SNPs in 35 genes in homologous recombination repair involved in DNA repair among healthy individuals[141]

PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism.