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A Case-control Study On The Polymorphism Of Gene XPD And The Risk Of Primary Hepatic Carcinoma In Liaoning Region

Posted on:2010-04-12Degree:MasterType:Thesis
Country:ChinaCandidate:X M CuiFull Text:PDF
GTID:2144360275981057Subject:Medical imaging and nuclear medicine
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Background and ObjectivePrimary hepatic carcinoma(PHC) is the malignancy of hepatic epithelium,consist of hepatocellular liver cancer,cholangiocellular carcinoma,and concoct cellular carcinoma.PHC is one of the most common maligmant tumor in china and takes the third place of the mortality in the gastric system,following gastric cancer and esophageal cancer.The mobidity of primary hepatic carcinoma(PHC) trend to ascend recent years causing two handred and fifty thoudsand death all over the world in which 47.3%are Chinese.The male have a high liability to PHC leading to a ratio of 2-5:1 between the male and female.The mobidity of primary hepatic carcinoma(PHC) has obvious regionally.It is higher in Asian male than in Northern Europe and Northern America male.It is higher in seaside region than inland in our courtry,and it is quite high in the Southerneast and Nourtheast.The study on the happening and developing and the prevention and treatment of the primary hepatic carcinoma(PHC) is paid close attention to fully for the universality and deep damage.DNA repair system is a chief defense barrier in vivo,taking part in repairing DNA injury caused by internal and outside environmental factors.The polymorphism of DNA repair gene may be the main reason of causing the individual differences of DNA repair ability and the increase of tumor susceptibility.XPD gene is one of the seven hereditary complementation genes encoding NER related proteins.XPD gene product is a kind of highly conservative ATP depended unwindase in transcription reparative factor TFIIH compounds,developing dual effects in NER and transcription.The mutation of the XPD gene can decreases the activities of its compounds,producing Asp312Asn.The XPD polymophism fuction is not very clear now.It may affect its protein synthesis, thus affect the interaction with p44,decrease unwindase activity.NER functional deficit cause the decease of DNA rapair ability,then the increase of tumor susceptibility.Our study understood that primary hepatic carcinoma(PHC) is related to the polymophism of XPD gene through detecting XPD polymophism of hepatic carcinoma patients and normal contrast control,explored the relationship of the polymophism of DNA repair gene XPD and primary hepatic carcinoma(PHC).Material and MethodThe experimental subjects composed of 94 cases with primary hepatocellular carcinoma and 111 healthy controls in Liaoning Province.All patients did not undertake chemoradiotherapy before blood collection.The normal control were matched by 1∶1 according to age,sex and case frequency.The demography material and related risk factor of each subject were collected while collecting blood samples.The polymorphism genetic type of Lys751Gln of XPD gene and Argl94Trp,Arg280His, Arg399Gls of XRCC1 gene were analyzed by PCR-RFLP.DNA were distilled from anticoagulated blood by potassium iodide.PCR amplified polymorphisms of XPD-751.The designed primer of each gene was as follows.XPD 751:5′-GCCCGCTCTGGATTATACG-3′and 5′-CTATCATCTCCTGGCCCCC-3′.The PCR reaction condition of XPD 751 XRCC1-194 and XRCC1-399 were 2min predenaturation at 94℃,then 30s at 94℃,30s at 57℃,45s at 72℃with 30 circulations as above and 7min extension at last.The condition of XRCC1-280 was the same except for changing 57℃to 59℃in the 30 circulations.Electrophoresis analyzed products of PCR.The products were incised by enzyme.The incision enzyme were Pst I for XPD-751.5μl PCR product was digested with corresponding restrictive endoneuclease over night.The enzymatic incised products were analyzed by 1.5%agarose gel electrophoresis.The distribution differences of polymorphisms of XPD751 and related risk between the case group and control group were analyzed by chi-square test.The relationship of polymorphism genotype with risk of hepatocellular carcinoma and interaction with exposed risk factor were analyzed by Logistic regression.SPSS16.0 was used for Statistic analysis. Results1,The frequence of polymorphism genotype of Lys/Lys,Lys/Gln,Gln/Gln of XPD751 gene in patients with hepatocellular carcinoma were 69(73.4%),24(25.5%) and(1.1%) respectively,which in the control group were 97(87.4%),14(12.6%) and 0(0%).The difference were highly significant between the groups(p=0.011).2,It was observed by Logistic regression analysis that the risk of suffering hepatocellular carcinoma increased significantly in individuals carrying at least one allele of 751Gln(Lys/Gln和Gln/Gln genotype)(OR=2.51,95%CI为1.22-5.181, p=0.011).ConclusionOur study discovered that XPD 751 site gene polymophism is related to PHC closely.The polymophism of XPD gene Lys751Gln is a factor of hereditary susceptibility in PHC.
Keywords/Search Tags:Hepatocellular carcinoma, DNA repair gene, XPD, Genetic polymorphism, Hereditary susceptibility
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