Font Size: a A A

A Molecular Epidemiological Study On The Relationship Between The Genetic Polymorphism Of CYP2E1,GSTP1 And Susceptibility To Esophageal Cancer

Posted on:2005-09-14Degree:MasterType:Thesis
Country:ChinaCandidate:W WangFull Text:PDF
GTID:2144360125451760Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
between the Genetic Polymorphism of CYP2E1, GSTP1 and Susceptibility to Esophageal CancerEsophageal cancer is one of the most dreaded diseases in China, displaying poor prognosis. However, early esophageal cancer without lymphnode metastases can be treated relatively easily and safely, for example, by endoscopic mucosal resection. Thus, early detection and early diagnosis are essential for improving the prognosis of esophageal cancer. To reach this target, a population-based molecular epidemiological study on esophageal cancer was conducted in the Nanjing areas of Jiangsu Provice.Part I The Relationship between Genetic Polymorphism of Cytochrome P4502E1(CYP2E1) and Susceptibility toEsophageal CancerThere are considerable evidences suggesting that human esophageal cancer is a multistage process with multiple risk factors. Alcohol consumption and smoking habit are major risk factors in low risk areas. CYP2E1, a member of the cytochrome P-450 superfamily, can be induced by ethanol and catalyses the oxidation of more 75 xenobiotic substrates, including ethanol itself, drugs, and several potential carcinogens(some nitrosamines, benzene, aniline et al) that ate transformed to their ultimatereactive forms. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was utilized to analyze the relationship between the polymorphic Rsal site in the 5'-regulatory region and Dral site in intron 6 of CYP2E1 with susceptibility to esophageal cancer. The results as following:1. The relationship between frequencies of CYP2E1 genotype and susceptibility to esophageal cancer.There were three genotypes of CYP2E1 resulting from digestion with restriction enzyme Rsal : type A, a wild-type homozygote c1/c1; type B, the heterozygote c1/c2; and type C, a mutant type homozygote c2/c2. In cases, the frequencies of A genotype, B genotype and C genotype are 61.5%, 30.8% and 7.7% respectively. In controls, the frequencies of A genotype, B genotype and C genotype are 50.8%, 35.6% and 13.6% respectively. There is not a significant difference in the frequencies of A, B and C genotypes(X2=2.170, P=0.141). As for the polymorphic and Dral site in intron 6 of CYP2E1, There is also not a significant difference in the frequencies of DD, CD and CC genotypes(X2=0.785, P=0.376).2. The combined effect between genetic polymorphism of CYP2E1 andsmoking ,drinking on esophageal cancerSubjects who had A genotype of CYP2E1 and smoking had 1.0 folds risk developing esophageal cancer compared with those who had B or C genotype of CYP2E1 and not smoking. Individuals exposed to Agenotype of CYP2E1 and not smoking had 1.9 folds risk developing esophageal cancer, and Individuals who had B or C genotype but had smoke habit had 2.0 folds risk developing esophageal cancer. So there is not finding combined effect between genetic polymorphism of CYP2E1 and smoking on esophageal cancer. The same to that, polymorphism of CYP2E1 and drinking have also not combined effect.Part II The Relationship between Genetic Polymorphism of glutathione S-transferase P1 (GSTP1) and Susceptibility toEsophageal CancerGSTs catalyze the binding of a large variety of electrophiles to the sulfydryl group of glutathione, are involved in the detoxification of radicals, and have a main function in the binding and transport of a wide variety of harmful compounds. GSTP1 is a major GST isoform expressed in human esophagus and has been shown to be genetically polymorphic. One single-base mutations within extrin 5 has been identified that result in lie-to-Val change in the amino acid sequence of the protein, which alter affinity and activity for some substrates of the enzyme. Therefore, the GSTP1 polymorphism may also have potential effects on cancer susceptibility. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was utilized to analyze the relationship between the polymorphic BsmAI site in extron 5 of GSTP1 withsusceptibility to esophageal cancer. The results as following:1. There were three genotypes of GSTP1 resu...
Keywords/Search Tags:Epidemiological
PDF Full Text Request
Related items