| Objectives Hepatocelullar carcinoma is a complex digestive system malignant tumor caused by the combination of genetic factors and environmental factors.At present,there is no effective treatment method.This paper investigates the effect of hMSH3 and hMSH2gene single nucleotide polymorphism and interaction with the environment on the susceptibility of hepatocelullar carcinoma.Finding the susceptibility factors of hepatocelullar carcinoma from genetics and environment,providing important evidence-based evidence for the identification of molecular markers,early diagnosis and clinical cure.Methods In this paper,case-control research methods were used to collect data and samples from hepatitis B virus-hepatocelullar carcinoma patients and hepatitis B patients in several top three hospitals and specialist hospitals.The genomic detection of the selected gene loci was carried out by SnapShot technology of American ABI,Excel2007 was used to establish the database,SPSS17.0 and MDR2.0 statistical softwares were used for data analysis,t test and?~2 test analysis single factor influence,fork analysis,logistic regression and multi-factor dimensionality reduction MDR analysis of interaction effects.Results 1 There were statistically significant differences in age,hepatitis B infection duration,drinking history and smoking history between case group and control group(P<0.05);2 The 10 loci of hMSH3rs1428030,rs1805355,rs181747,hMSH2rs2303428were in accordance with Hardy-Weinberg's genetic equilibrium law(P>0.05).The frequency distributions of hMSH3rs1428030 locus AA,AG and GG genotypes in case group and control group were 39.4%,54.5%,6.1%,and 45.5%,37.9%,and 16.7%,significant differences between the two groups(?~2=16.61,P<0.001);The frequency of genotypes of hMSH3 rs1805355 in GG,AG,and AA in the case group were 39.4%,54.5%and 6.1%,in control group were 45.5%,37.9%,and 16.7%,significant differences between the two groups(?~2=16.61,P<0.001).hMSH3 rs181747 in the case group The frequencies of AA,AG and GG were 34.8%,59.1%and 6.1%,the genotype frequencies in the control group were 47.0%,37.9%and 15.2%,significant differences between the two groups(?~2=20.46,P<0.001).In the case group hMSH2 rs2303428 genotype frequencies of TT,CT and CC were 33.3%,56.1%and 10.6%,in the control group they were48.5%,37.9%and13.6%,significant differences between the two groups(?~2=13.27,P<0.001);3 After adjusting for factors such as age,HBV infection duration,drinking and smoking,multivariate logistic regression analysis found that individual with GG genotype at hMSH3rs1428030 had the possibility of HBV-HCC with an AA genotype of 0.39(95%CI:0.16~0.93)times;AG and AA genotypes at hMSH3rs1805355 were 2.84(95%CI:1.17~6.89)and 4.17(95%CI:1.70~10.21)times that of GG genotype at risk of HBV-HCC,respectively;the probability of HBV-HCC in individuals carrying the AG genotype at hMSH3 rs181747 was 2.05(95%CI:1.17~3.61)times of AA genotype;There was no significant difference in genotype distribution hMSH2 rs2303428,but the dominant and codominant models were statistically significant(P<0.05);4 In gene-gene interaction,logistic regression showed that hMSH3rs1428030 and rs1805355 had interaction based on multiplicative models(P<0.05);three models of multifactorial dimensionality reduction MDR method showed no interaction between genes-genes;5 In gene-environment interaction,the fork analysis and the multiplicative model showed that there was an interaction based between the hepatitis B infection duration and the polymorphism of every gene;Drinking interact with hMSH2rs2303428,smoking interactions based on the multiplicative model with drinking,rs1805355 and hepatitis B infection duration;Multi-factor dimensionality reduction MDR method display that HBV infection duration,hMSH3rs181747 and hMSH2rs23034283 factors model is statistically significant(P=0.006<0.05),the test sample accuracy was 71.98%,and the cross-validation consistency reached 100%.It can be considered that there is an interaction between HBV infection duration,rs181747 and rs2303428 in the pathogenesis of hepatitis B virus-hepatocellular caecinoma,the interaction value is 6.67(95%CI:1.65~26.89).Conclusions 1 hMSH3 rs1428030,rs1805355,rs181747 and hMSH2 rs2303428 gene polymorphisms are associated with HBV-HCC susceptibility;2 hMSH3 rs1428030 and rs1805355 multiplicative model interactions are associated with HBV-HCC susceptibility;3 Individuals with a history of HBV infection,drinking history,smoking history,and hMSH3 rs1428030,rs1805355,rs181747 and hMSH2 rs2303428 site defects can increase the risk of HBV-HCC;4 Meta-analysis showed that the CC and CT genotypes of hMSH2rs2303428 locus in the population were considered to be risk factors for tumors.Figure10;Table24;Reference 116... |
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