Association Between Polymorphisms Of IL-2 Gene Rs2069763,IL-10 Gene Rs1800872 And Hepatitis B Virus-related Hepatocellular Carcinoma

Background and Objective:Hepatitis B virus-related hepatocellular carcinoma(HBV-related HCC)is a heterogeneous disease,and the incidence of it is increasing in China.Multiple studies showed that interleukin-2(IL-2)and interleukin-2(IL-10)were associated with susceptibility to HBV-related HCC.HBV-related HCC is a complex disease,and the multistep process involved in multiple genes and environmental factors.In China,about 90%of HCC patients with HBV infection background.After HBV infection,a long time viral replication activity will cause chronic inflammation in liver,stimulate regeneration of blood vessels,damage DNA,and stimulate the growth of malignant tumor cells,thus lead to tumorigenesi.But the exact mechanism mechanisms linking HBV infection and HCC remain an open question Single nucleotide polymorphism(SNP)is an important factor that would influence the genetic susceptibility of individuals.At present,there are different opinions about the association between IL-2 SNP,IL-10 SNP and the risk of HBV related HCC.This study selected IL-2 gene rs2069763 and IL-10 gene rs1800872 for exploring the relationship between these 2 SNPs and the susceptibility of HBV related HCC,furthermore,exploring the interaction between the two SNPs..Methods:From November 2014 to August 2016,we enrolled 263 HBV-related HCC patients(216 men)and 350 healthy controls(284 men)from Qingdao Municipal Hospital.Venous blood samples of each subject for biochemical and Genetic Analysis were obtained and collected.The genetic analysis of IL-2 SNP rs2069763 and IL-10 SNP rs1800872 was using sequencing and polymerase chain reaction analysis(PCR)and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry(MALDI-TOF MS).And the basic clinicopathological informations were obtained at the same time.Statistical analysis for Pearson Chi square test,t test and logistic regression analysis were performed using SPSS software,version 19.0 for Windows.Generalized multifactor dimensionality reduction(GMDR)was applied to explore the effect of SNP-SNP interactions on the risk of HBV-related HCC.Results:There were no significant differences in age,gender,tobacco consumption status or alcohol consumption status between HBV-related HCC patients and the healthy controls(P>0.05).Compared to the controls,HBV-related HCC patients had higher serum levels of serum total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),y-glutamyltransferase(GGT),and lower levers of total protein(TP)and albumin(ALB)(all Ps<0.05).The genotype and allele frequencies of the IL-2 and IL-10 polymorphisms between the HBV-related HCC group and the healthy control group were significantly different(all Ps<0.05).In the logistic regression analysis adjusted for gender,age,smoking and drinking,the carriers of the rs2069763 G allele,and rs1800872 G allele had significantly increased susceptibility to HBV-related HCC(OR,1.541,95%CI,1.053 to 2.256,P=0.026,OR,1.402,95%CI,1.011 to 1.943,P=0.043,respectively).After adjusted for gender,age,smoking and drinking,the results were still significantly(OR,1.605,95%CI,1.090 to 2.364,P=0.005;OR,1.465,0.579,95%CI,1.052 to 2.041,P=0.006,respectively).Moreover,in HCC group,compared to noncarriers,the rs2069763 G allele carriers have significantly higher levels of aspartate aminotransferase(AST)and alkaline phosphatase(ALP)(P = 0.001 and P<0.001);and the carrier of G allele of rs1800872 had higher levels of alanine aminotransferase(ALT),AST and ALP(P = 0.020,P =0.011,P = 0.024,respectively).Further,the GMDR analysis indicated that a interaction between rs2069763 and rs1800872 might not exist,and the combination effect of the two SNPs may not contributes to the risk of HBV-related HCC.Conclusion:We demonstrated that rs2069763 G allele in IL-2 gene and rs1800872 G allele in IL-10 gene created susceptibility to HBV-related HCC in a Chinese Han population.The combination of the rs2069763 in IL-2 gene and rs1800872 in IL-10 gene may not have the interaction to predict the predisposition to HBV-related HCC.