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Association Between DNA Repair Gene Polymorphisms And Environmental Factors And Hp-associated Gastric Cancer And Duodenal Ulcer

Posted on:2012-09-02Degree:MasterType:Thesis
Country:ChinaCandidate:Z H LiFull Text:PDF
GTID:2214330338469672Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background and purposes:Helicobacter pylori (Hp) infection is a major cause of duodenal ulcer, is also class I carcinogen of gastric cancer.However, patients with duodenal ulcer rarely suffer gastric cancer.and the two diseases rarely coexist.the outcome of the inconsistency after Hp infection is the result of host genetic susceptibility,Hp and environmental factors. Hp infection can caues DNA damage by oxidative damage or inducing host inflammatory response,DNA repair enzymes play an important role on the repair of DNA damage,gene polymorphisms of the DNA repair enzyme may affect the outcome of Hp infection.Therefore, to observe the distribution of DNA repair genes APE1, XRCC1 and XPG polymorphisms in helicobacter pylori(Hp) associated gastric cancer and duodenal ulcer patients of Jiangxi province in this study, select genetic susceptible genotypes of Hp-associated gastric cancer,and study environmental factors of Hp-associated gastric cancer and duodenal ulcer,analyze the interaction of genetic susceptible genotypes and environmetal factors between Hp infected gastric cancer and environmental factors.Methods:Subjects were divided into two groups,one group was the Hp-positive non-cardia gastric cancer patients,the other was excluding NSAID Hp-positive duodenal ulcer patients. Selected 5 polymorphsims of DNA repair genes APE1,XRCC1 and XPG5 were analyzed.Used quick whole blood genomic DNA extraction kit (solution type) to extract DNA.By using MALDI-TOF mass spectrometry, analyzed the genotypes on various gene loci,and calculated genotype and allele frequencies of different groups, analyzed the association and its strength (OR value) between genotype and allele and gastric cancer by using single factor non-conditional Logistic regression analysis. At the same time, investigated the environmental factors, mainly including smoking history, drinking history and family history, and analyzed the contribution of gene polymorphsims and environmental factors on susceptibility of Hp-associated gastric cancer. Results:1.In the site of APE1 Asp148Glu,the frequence of polymorphism genotype of TT,TG and GG in patients with Hp-associated gastric cancer were 21%,51%,29%respectively,which in the control group were 36%,45%,19%.The difference were significant between the two groups (P=0.013).2.It was observed by single factor non-conditional Logistic regression analysis that the risk of suffering Hp-associated gastric cance increased significantly in individuals carrying at least one G allele (APE1148TG and APE1148GG genotypes) (OR=2.154,95%CI:1.253-3.701,P=0.005).3. In the site of APE 1 Ile64Val,the frequence of polymorphism genotype of A A, GA and GG in patients with Hp-associated gastric cancer were 88%,10%,2%respectively,which in the control group were 88%,10%, 1%.The two groups had no significant difference (P=0.774).4.The risk of suffering Hp-associated gastric cancer did not have significant increase between individuals carring GA, GG genotypes compared with AA genotype by Logistic regression analysis(OR=0.965,95%CI:0.465-2.002, P=0.924).5. In the site of XRCC1 Arg194Trp,the frequence of polymorphism genotype of CC, CT, TT in patients with Hp-associated gastric cancer were 44%,50%,6%respectively,which in the control group were 44%,44%,12%.The two groups had no significant difference ((P=0.281).6. The risk of suffering Hp-associated gastric cancer did not have significant increase between individuals carring CT, TT genotypes compared with CC genotype by Logistic regression analysis(OR=0.977,95%CI:0.609-1.568, P=0.922).7. In the site of XRCC1 Arg399Gln,the frequence of polymorphism genotype of GG,GA and AA in patients with Hp-associated gastric cancer were 40%,44%,16%respectively,which in the control group were 56%,34%,10%.The difference were significant between the two groups (P=0.022).8. It was observed by single factor non-conditional Logistic regression analysis that the risk of suffering Hp-associated gastric cancer increased significantly in individuals carrying at least one A allele (XRCC1-399 GA and XRCC1-399 AA genotypes) (OR=1.917,95%CI:1.190-3.087, P=0.007).9. In the site of XPG Asp1104His,the frequence of polymorphism genotype of GG,GC and CC in patients with Hp-associated gastric cancer were 26%,50%,24%respectively,which in the control group were 44%,21%,52%.27%.The two groups had no significant difference (P=0.585).10. The risk of suffering Hp-associated gastric cancer did not have significant increase between individuals carring GC,CC genotypes compared with GG genotype by Logistic regression analysis(OR=0.428,95%CI:0.720-2.171,P=0.428).11.The independent risk factors of Hp-associated gastric cancer was smoking (OR=2.024, 95%CI was 1.412-4.28) by non-conditional Logistic regression multivariate analysis in Jiangxi province.12.1nteration existed between APE1 Asp148Glu and XRCC1 Arg399G1n.The risk of suffering Hp-associated gastric cancer increased in individuals carrying APE1 TT and XRCC1 GG compared with carrying APE1 GG genotype and XRCC1 AA(OR=7.778,95%C1:1.448-41.780).13. Interation existed between APE1 Asp148Glu and XRCC1 Arg399Gln with smoking. In the site of APEl Asp148Glu,the risk of suffering Hp-associated gastric cancer increased in smoking individuals carrying TG+GG genotype compared with the TT genotype(OR=2.489, 95%CI:2.25-5.057,P=0.012). In the site of XRCC1 Arg399Gln,the risk of suffering Hp-associated gastric cancer increased in smoking individuals carrying GA+AA genotype compared with the GG genotype(OR=3.472,95%CI:1.786-6.749,P=0.000).Conclusions:1.APEl Aspl48Glu gene polymorphism was a susceptible factor of Hp-associated gastric cancer,G allele was a risk gene for gastric cancer.2.XRCCl Arg399Gln gene polymorphism was a susceptible factor of Hp-associated gastric cancer,A allele was a risk gene for gastric cancer.3.APE1 lle64Val,XRCCl Arg194Trp,XPG Asp1104His genetic polymorphsim had no relationship with susceptibility of Hp-associated gastric cancer.4.Interaction existed between APEl Asp148Glu and XRCCl Arg399Gln gene polymorph-isms and smoking in Hp-associated gastric cancer.
Keywords/Search Tags:Hp infection, DNA repair genes polymorphism, environmental factors, gastric cancer, duodenal ulcer
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