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Polymorphisms Of The DNA Repair Genes HOGG1 And MBD4 In Chinese Population And Their Associations With Risk Of Hepatocellular Carcinoma

Posted on:2004-08-02Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2144360095450108Subject:Oncology
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BackgroundHepatocellular carcinoma (HCC) rank third in frequency in China. The pathogenesis of HCC is atill under discussion. Many reports show that the pathogenesis of HCC was strong associated with environmental factor, including hepatitis B virus (HBV) infection, alcohol consumption, smoking and carcinogens exposure (aflatoxin, for example). But only a few people developed HCC even though they live in the geographic areas at highest risk of HCC or they are HBV infected. This suggests that the individual susceptibility plays a in portent role in the pathogenesis of HCC. The susceptible genetic marker of HCC is not clear. We know that the NDA of HBV codes a protein HBX. HBX inhabits the rejoining of DDB1 with DNA. In the DNA repair system, DBB1 is very important. HBX reduces the repairing capability of the DNA repair system. The EST analysis show a lower expression of DNA repair genes in HCC. A low frequency of HCC was observed in mousse with over expression of MGMT, a DNA repair gene. These suggest that HBV may induce HCC by inhabiting the DNA repair system. The DNA repair genes play a import role in the pathogenesis of HCC.DNA repair system continuously monitor chromosome to protect the integrity of DNA. There four main DNA repair pathways. The base excision repair (BER) pathway is one of them. BER excise and replace damaged DNA base. DNA glycosidase initiate this process by releasing the modified base. This is followed by cleavage of the sugar-phosphate chain, excision of the basic residue, and local DNA synthesis and ligation.hOGG1 gene and MB04 gene are among the genes of glycosidase. Study on the association between HCC and these two genes may help us to better understand the pathogenesis of HCC, and provide theoretical ways to prevent, diagnose and treat HCC.Material and Method1. Material96 HCC patients and 96 healthy controls were enlisted. All patient and healthy controls were enlisted. All patients and healthy controls come from Henan. The data such as smoking, alcohol consumption and HBV infection were recorded. 5ml ofperipheral blood was taken from each patient and healthy control. The blood sample were mixed with sodium citrate and preserved at -20℃.2. MethodAfter DNA was extracted from the blood sample,Ser326Cys and Clu346Lys,the polymorphic Loci of hOGG1 and MBD4 gene, were amplified by Polymerase Chain reactions (PCR). after the application was identified by gel electrophoresis, the amplified DNA strips were purified. Then the Ser326Cys and Clu346Lys polymorphisms in the two groups were detected by DNA analysis. Polyphred, a software, was used to analysis and determine the association between these genetic polymorphisms and risk of HCC.Protocol:Peripheral blood→ DNA extraction→ PCR application→Gel electrophoresis→ Purification→ DNA analysis3. Statistic analysisThe relative risk was expresses as odds rations (ORs) and 95% confidence intervals (CIs).All statistic tests were two sided. Statistic Analysis (SAS,SAS institute, Cary, NC, USA) was used.Results3 genotypes (Ser/Ser, Cys/Ser, and Cys/Cys) were found in exon 7 of the hOGGi. The frequency of allelic hOGGi gene in HCC patients were high than that of control group (43% vs 3 Irrespectively). In the HCC group, the frequencies of Cys/Cys, Cys/Ser , and Ser/Ser were 20.9%,44.2%,and 34.9% respectively. Compared with the control group, the frequency of genotype Cys/Cys and Cys/Ser were lower than in the HCC group, while the Ser/Ser genotype was higher, it was show, the risk of HCC were about 2 times higher in patient with Cys/Cys genotype ( OR=1.9). The frequency of allele Cys in the HCC group was significantly higher than in the control group (43% vs 33.1% respectively)3 genotypes (Glu/ Glu, Glu /Lys, and Lys / Lys) were found in exon 3 of the MBD4 gene. In the control group the frenquency of genotype Glu/ Glu, Glu /Lys, and Lys / Lys were 40.4%,46.8%,12.8% respectively while in the HCC group. They were 41.7%,48.8% and 9.5%. There were no significant difference in the frequency of...
Keywords/Search Tags:Hepatocellular
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