A Study On The Relationship Between Single Nucleotide Polymorphisms Of ERCC1,TNF-? And The Susceptibility To Hepatocellular Carcinoma In Guangxi Zhuang Population

ObjectiveAt present,in the study of single nucleotide polymorphisms of hepatocellular carcinoma and susceptibility to hepatocellular carcinoma in DNA repair gene is a major research hotspots.Excision repair cross complementing 1(ERCC1)is one of the key genes of the nucleotide excision repair pathway,the gene polymorphisms of ERCC1 may affect the ability of DNA excision repair and lead to the occurrence of cancers.In the process of tumorigenesis,most of the patients with chronic inflammatory diseases,when chronic inflammation is persistent,The incidence of tumor increased significantly.Therefore,cytokines are also important factors in the occurrence and development of hepatocellular carcinoma the one of the most popular cytokines including tumor necrosis factor.This research mainly discusses the relationship between the single nucleotide polymorphisms of ERCC1-4533/-8092 and TNF-?-238/-308 and expression of ERCC1 m RNA in blood,serum TNF-? levels and Guangxi Zhuang population susceptibility to hepatocellular carcinoma and its clinical significance.Methods1:1 case-control study was conducted in 80 patients with hepatocellular carcinoma.The control group was admitted to the hospital in the same period.There were 80 cases of non-tumor patients matched by age and sex in the control group.Polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)was used to analysis the single nucleotide polymorphisms of ERCC1-4533/-8092,TNF-?-238/-308.The expression level of ERCC1 in blood was detected by real-time quantitative reverse transcription polymerase chain reaction(q RT-PCR).Enzyme linked immunosorbent assay(ELISA)detection of serum TNF-? levels.Statistical analysis using SPSS17.0 software.The Hardy Weinberg equilibrium test was used to determine whether the genotype distribution of the control group was representative and comparable.Independent sample T test was used to analyze the basic information of the research objects.Variance analysis was used to analyze the distribution of single nucleotide polymorphisms and the difference of alleles between HCC group and control group.Rank sum test was used to analyze the relationship between single nucleotide polymorphism and gene expression.Non-conditional Logistic regression method of statistical analysis was adjusted for gender,age,smoking,alcohol consumption,the positive rate of HBs Ag and other confounding factors,calculated the odds ration(OR)and 95% confidence interval(95% CI).When P<0.05,the difference was statistically significant.Results1.the genotype distribution frequencies of ERCC1-4533 and 8092,TNF-?-238 and 308 in the hepatocellular carcinoma group were consistent with the Hardy-Weinberg's law of genetic equilibrium(P>0.05).2.Statistical analysis of single nucleotide polymorphisms and gene expression of ERCC1 and susceptibility to hepatocellular carcinoma:There was no significant difference in the frequency distribution of ERCC1-4533 genotype and allele frequency in the HCC group and control group(P>0.05).The ERCC1-8092 genotype had significant difference in frequency distribution of the HCC group and control group(P<0.05).ERCC1-4533 polymorphisms were not associated with susceptibility to hepatocellular carcinoma(OR=1.574,95% CI:0.495-5.003).Compared with the ERCC1-8092 CC genotype,carrying ERCC1-C8092 CA/AA genotype has higher susceptibility to hepatocellular carcinoma(OR=3.255,95% CI:1.954-11.105).The expression level of ERCC1 m RNA in blood of the HCC group was higher than that of control group(P<0.05),and the expression level of ERCC1 m RNA was not related to genotypes(P>0.05).3.Statistical analysis of single nucleotide polymorphisms and gene expression of TNF-? and susceptibility to hepatocellular carcinoma : TNF-?-238 genotype and allele frequency in no significant difference in frequency distribution of the HCC group and control group(P>0.05).TNF-?-308 genotype had significant difference in frequency distribution of teh HCC group and control group(P<0.05).The TNF-?-238 polymorphisms were not associated with susceptibility to hepatocellular carcinoma(OR=0.831,95%CI:0.180-3.824).Compared with the TNF-?-308 GG genotype,carrying TNF-?-308 GA/AA genotype with higher susceptibility to hepatocellular carcinoma(OR=5.288,95% CI:1.287-21.734).The level of serum TNF-? in patients with primary hepatocellular carcinoma was significantly higher than that in control group(P<0.05),and the level of serum TNF-? of TNF-?-308 GA/AA Genotype was higher than those of TNF-?-238 GG(P<0.05).ConclusionThe levels of ERCC1 m RNA and serum TNF-? in patients with primary hepatocellular carcinoma were higher than those in control group.Single nucleotide polymorphisms of ERCC1-8092 and TNF-?-308 may be associated with susceptibility to hepatocellular carcinoma in Guangxi Zhuang population.