Association between variant alleles of major histocompatibility complex class II regulatory genes and nasopharyngeal carcinoma susceptibility

Major histocompatibility complex (MHC) class II regulatory genes play a paramount role in immune response that can exert a predominant influence on clinical outcome of Epstein-Barr virus infection consistently assumed as the main pathogenetic factor for nasopharyngeal carcinoma. To elucidate the relationship between allelic variants ofMHCclass II regulatory genes and susceptibility to nasopharyngeal carcinoma, a total of 28 polymorphic loci atMHCclass II regulatory genes, involvingCIITA,CREB1,RFXfamily genes (RFX5,RFXAP,andRFXANK), andNFYfamily genes(NFYA,NFYB, andNFYC), were genotyped by multiplex SNaPshot minisequencing in 137 patients with nasopharyngeal carcinoma and 107 healthy controls from the southern Chinese population. Allelic analysis disclosed that rs7404873, rs6498121, rs6498126, and rs56074043 shared correlations with nasopharyngeal carcinoma (P-trend< 0.05). Further, rs6498126 onCIITAwas independently associated with the risk of developing nasopharyngeal carcinoma (CC vs. GG, odds ratio: 7.386, 95% confidence interval: 1.934-28.207,P-trend< 0.01). Conversely, rs7404873 onCIITAand rs56074043 onNFYBmanifested epistatic interaction to decreased susceptibility of nasopharyngeal carcinoma (rs7404873, TT vs. GG, odds ratio: 0.256, 95% confidence interval: 0.088-0.740,P-trend< 0.05; rs56074043, AA vs. AG, odds ratio: 0.341, 95% confidence interval: 0.129-0.900,P-trend< 0.05). Additionally, bioinformatics analysis revealed that the three variants were transcriptional regulatory in function and might impact the expression of nearby genes. The findings suggested genetic variants onMHCclass II regulatory genes contributed to nasopharyngeal carcinoma susceptibility and might provide new insights for screening high-risk population.