Study On The Relationship Between Mismatch Repair System MLH1&hMSH2Polymorphisms And Hepatoceilular Carcinoma

Objective: To study the relationship between mismatch repair system MLHIand hMSH2polymorphisms and hepatoceilular carcinoma. To explore thedistribution frequency and characteristics of three common single-nucleotidepolymorphisms (SNPs) of MLHI and hMSH2of people in GuangXi province,This study also focus on the interaction between the genotypes and cancerfamily history, smoking, alcohol consumption, HBV,and genes occurred inHCC, aiming at understanding of pathogenesis of HCC, searching forindividual susceptibility of molecular markers, so as to provide new ideas and atheoretical basis for the mechanism of HCC and comprehensive preventionmeasures from a new point of view.Methods: A population based case-control study and Polymerase ChainReaction(PCR) method are conducted, which is used to analyze SNP of MLHIand hMSH2gene associated with the incidence and development of HCC.Collection of453HCC case samples and475control samples. We havecollected the clinical data of all the volunteers, which is used to finish a databasefor further study. We have collected the blood samples of all the volunteers andextracted DNA kept in-80℃refrigerator. Newly histopathologicallydiagnosed HCC patients were recruited from Affiliated Hospital of GuilinMedical University, NanXiShan Hospital of Guangxi and Tumor Hospital ofGuangxi Medical University. Controls were recruited in health screening centerin the same hospitals, with the case and the control matched in terms of ages,sex, and habitation. And all the subjects were surveyed face to face by the specifically trained investigators. The questionaire features include basic datum,disease history, personal history, family history, smoking history, and drinkinghistory etc.2ml fasting venous blood were collected at the second day morning,and genome DNA were extracted at the same day. All the subjects had signedthe study consensus protocol MLHI and hMSH2polymorphisms weredetermined by polymerase chain restriction with TaqMan MGB probe. All datawere analyzed by conditional logistic multiple factor regression analysis withSPSS19.0statistical package.Results: Valid questionnaires:453case group and475control group. In casegroup minimum age is21, maximum age is75. The average age is47.6±10.3. Incontrol group minimum age is22, maximum age is72. The average age is46.8±11.8. The difference of age, gender in the two groups has no statisticalsignificance by balance test (p>0.05).(1) It is statistically significant in thefrequencies of hMLH1rs1800734AA, AG and GG genotype between case andcontrol (P=0.001). The odds risk of AG and GG genotype compared to AA are1.033(95%CI=0.778-1.371) and1.842(95%CI=1.242-2.733). The frequenciesof AG/GG genotype in case are significantly lower than in control(X2=4.194,P=0.041), OR=1.323（95%CI=1.012-1.729).(2) It is statisticallysignificant in the frequencies of hMSH2（rs2303428）CC, CT and TT genotypebetween case and control (P=0.016). The odds risk of CT and TT genotypecompared to CC are1.811(95%CI=1.167-2.809) and1.874(95%CI=1.199-2.929). The frequencies of CT/TTgenotype in case aresignificantly lower than in control (X2=8.229,P=0.004), OR=1.839（95%CI=1.207-1.802).(3) It is statistically significant in the frequencies ofhMSH2rs4952887CC、 CT and TT genotype between case and control(P=0.035). The odds risk of CT and TT genotype compared to CC are0.740 (95%CI=0.543-1.007) and1.636(95%CI=0.855-3.132). The frequencies ofCT/TT genotype in case are significantly lower than in control(X2=1.394,P=0.238), OR=0.841（95%CI=0.630-1.122).(4) It is statisticallysignificant in the frequencies of hMSH2rs2059520GG, GT and TT genotypebetween case and control (P=0.273). The odds risk of GT and TT genotypecompared to GG are1.192(95%CI=0.909-1.562) and1.434(95%CI=0.797-2.580). The frequencies of CT/TT genotype in case aresignificantly lower than in control (X2=2.229,P=0.135), OR=1.219（95%CI=0.940-1.582）.(5) There are interactions among hMLH1（rs1800734）and family history of cancer, HBsAg positive. The interactions are also inhMSH2（rs2303428）.The interactions is not existed in hMSH2(rs4952887,rs205952).(6) Gene-gene interactions analysis claims that there are interactionsbetween hMLH1（rs1800734）and hMSH2（rs2303428）. There are not in otherlocus.Conclusions: The MLHI&hMSH2may contributes to the risk of HCC in southGuangxi. Interactions among family history of cancer, HBsAg positive andMLHI&hMSH2polymorphisms in the occurrence of HCC existed and it mayhave contributions to the risk of suffering HCC.