Study On Association Between TNFAIP3 Gene Polymorphism And Nasopharyngeal Carcinoma Susceptibility In Chinese Han Population

Objective: Epstein Barr virus(EBV)is closely associated with the occurrence and development of nasopharyngeal carcinoma(NPC).Late membrane protein 1(LMP1)plays an important role in the pathogenesis of NPC by mediating NF-κB signaling pathway.As a ubiquitin-editing enzyme,tumor necrosis factor alpha inducible protein 3(TNFAIP3)acts as a negative regulator in NF-κB signaling pathway and can down-regulate the activity of NF-κB.In recent years,several studies based on the existing genome wide association study(GWAS)and whole exome sequencing(WES)of Chinese Han population have shown that gene variation of TNFAIP3 in NF-κB signaling pathway is significantly associated with the pathogenesis of NPC,which may be the susceptibility gene of NPC.The aim of this study was to explore the relationship between single nucleotide polymorphism(SNP)of TNFAIP3 gene and susceptibility of NPC in Chinese Han Population,so as to explore the possible genetic pathogenesis of NPC and provide new ideas for early diagnosis and prevention of NPC in high-risk population.Methods: A total of 400 NPC patients pathological diagnosed for the first time at Sichuan Cancer Hospital and Sichuan Provincial People’s Hospital from January 2017 to December 2018 were recruited.The control group contained 550 healthy individuals were recruited from physical examination center of Sichuan Provincial People’s Hospital during the same period.The susceptibility gene TNFAIP3 in NF-κB signaling pathway was searched through KEGG(Kyoto Encyclopedia of genes and genomes)and NCBI(National Center for Biotechnology Information)databases,after using Online Mendelian Inheritance in Man(OMIM)to further clarify the association between TNFAIP3 gene function and NPC pathogenesis,the appropriate SNP sites of TNFAIP3 gene were screened from Ensemble,db SNP,1000 Genomes Project and Ex AC(Exome Aggregation Consortium).Finally,SNP rs2230926 was selected in TNFAIP3 gene.DNA was extracted from peripheral venous blood leukocytes by using kit.The concentration of all samples was higher than 20 ng/μL and OD 260/280 value was between 1.8 and 2.0.SNP rs2230926 was genotyped by Agena Mass Array,and Sanger sequencing was used to verify the genotyping results.Plink 1.03 software was applied to statistically analyze the allele frequency of rs2230926 between the two groups.Logistic regression analysis was used to calculate p value,odds ratios(ORs)and 95%confidence intervals(CIs)to evaluate the association between specific genotypes and NPC risk.All statistical tests were bilateral tests,and P < 0.05 was considered to be statistically significant.Results: SNP rs2230926 with Minor Allele Frequency(MAF)≥ 10% was consistent with Hardy-Weinberg(HWE).After removing samples which failed to be genotyped,a total of 388 NPC patients and 526 healthy controls were included in the statistical analysis.The GT genotype frequency was lower in the case group than that in the control group,with no statistical difference(OR 1.029,P = 0.908);the GG genotype frequency was lower in the case group than that in the control group,with no statistical difference(OR 2.225,P = 0.489).There was no statistical difference in genotype frequency between the case and control groups in the dominant model TT and GG+GT(OR 0.938,P = 0.938);and there was also no statistical difference in genotype frequency between the two groups in the recessive model TT+GT and GG(OR 2.220,P = 0.491).Conclusion: SNP rs2230926 of TNFAIP3 gene may not be associated with the susceptibility of NPC in Chinese Han population under the experimental conditions and statistical assumptions of this study.