| Lung cancer was one of the most common malignant tumors. The incidence and mortality of lung cancer in China have increased rapidly in recent years and the speed was in the first place in malignant tumors. Development of lung cancer was related to not only exposure of environment but also genetic polymorphisms.hOGG1(human 8-hydroxyguanine glycosylase, hOGG1) was one kind of DNA repair enzymes, which can repair DNA lesion by specially exciting 8-hydroxygen guanine. It was reported that C/G polymorphism of hOGG1 gene within 1245 base of exon 7 can lead to the fact that the codon 326 encode either serine or Cysteine. It was found in vitro that activity in the repairing 8-OH-G was significantly lower in hOGG1-Cys protein than in hOGG1-Ser protein. Therefore, individuals carring hOGG1-Cys were probably susceptible to tumor for their lower or deficit of capacity of repair.p53 was a tumor suppressor gene involved in lung cancer, which has been extensively studied in recent years. p53 play a key role in cell cycle control and in apoptosis. One of the important function of p53 was repairing cell lesion or inducing cell apoptosis. The CGC/CCC polymorphism of p53 within codon 72 of exon 4 canlead to the change of amino acid from arginine to proline, which was probably related to genetic susceptibility to certain tumor.In this study, polymorphism of hOGG1, codoning 326 Ser/Cys and p53, codon 72 Arg/Pro were investigated in the group of lung cancer and the control by PCR-RFLP to study the relationship of genetic polymorphisms and susceptibility to lung cancer and provide the theoretical base for screening and inteveneing high risk population of lung cancer. Materials and methods:1 Samples collection: 124 tissue samples were collected from cases with lung cancer including 101 males and 23 females from Henan Han people, whose ages ranged from 23 to 80. These patients hadn't undergone Radiation therapy and Chemical therapy before operation, without other malignant tumors history. Meanwhile 128 peripheral blood samples of healthy people were collected as controls, including 100 males and 28 females from Henan Han people, whose ages ranged from 35 to 83.2 Genotypes analysis: To amplify target fragments by PCR and to test polymorphism of hOGG1 codon 326 Ser/Cys and p53 gene codon 72 Arg/Pro by SatI and Bshl2361 using RFLP.3 Process the data using chi-square test, Hardy-Weinberg Equilibrium test and unconditional logistic regression test of SPSS 10.0. Test level a was equal to 0.05. Results:1 Polymorphism of hOGG1 codon 326 Ser/Cys and genetic susceptibility to lung cancerThe frequencies of allely gene Cys were 37.5% in cases and 39.9% in controls, respectively, the difference was not significant between two groups (P>0.05) . The frequencies of Cys/Cys genotype were 19.4% in cases and 10.2% in controls, respectively, there was statistical significance between two groups(P<0.05). Cys/Cys mutant genotype has increased the risk of lung cancer and the adjusted OR(95%Cl) was 2.28(1.07-4.86). The adjusted OR to squamous cell carcinomas,adenocarcinomas, and other type carcinomas were 2.61, 1.97, 3.12, respectively. The difference of Cys/Cys mutant genotype in pathology type was not significant.The risk of lung cancer increased more than respective effect for the smoking individuals with mutant genotype. For the smokers with non-mutant genotype, the adjusted OR(95%CI) was 2.28(1.18—4.40). For non-smokers with mutant genotype, the adjusted OR(95%CI) was 1.73(0.62—4.85). For the individuals with smoking and mutant genotype, the adjusted OR(95%CI) was 7.53(2.16 ~ 26.26). Interaction between smoking and Cys/Cys mutant genotype was observed.2 Polymorphism of p53 gene codon 72 Arg/Pro and genetic susceptibility to lung cancerThe frequencies of allely gene Pro were 46.4% in cases and 38.3% in controls, respectively, the difference was not significant between two groups (P>0.05) . The frequencies of Pro/Pro genotype were 28.2% in cases and 15.6% in controls, respectively, there was statistical difference between two groups (P<0.05) . Pro/Pro mutant genotype has increased the risk of lung cancer and the adjusted OR(95%CI) was 2.11(1.12-3.97). The adjusted OR to squamous cell carcinomas, adenocarcinomas, and other type carcinomas were 1.98, 3.65, 1.81, respectively. The difference of Pro / Pro mutant genotype in pathology type was not significant.The risk of lung cancer increased more than respective effect for the smoking individuals with mutant genotype. For the smokers with non-mutant genotype, the adjusted OR was 2.27(1.13 ~ 4.54). For non-smokers with mutant genotype, the adjusted OR was 0.93(0.36—2.38). For the individuals with smoking and mutant genotype, the adjusted OR was 10.49(3.42—32.23). Interaction between smoking and Pro/Pro mutant genotype was observed. For the individuals with smoking ≥604 cigarette year and Pro/Pro mutant genotype, the adjusted OR (95%CI) was 42.00(5.19-339.75).3 The interaction among genes and smoking on susceptibility to lung cancerTested by unconditional logistic regression, the adjusted OR (95%CI) for respective effect were 2.00(1.00-4.01) and 2.06(0.86-4.95) for p53 Pro/Pro and hOGG1 Cys/Cys, respectively. The adjusted OR (95%CI) for their combined effect was 3.95(1.02~ 15.40) . No interaction between hOGG1 Cys/Cys genotype and p53 Pro/Pro genotype was observed. Interaction among smoking, hOGG1 Cys/Cys genotype and p53 Pro/Pro genotype was not found. Correlation between smoking and lung cancer was higer than that between genes and lung cancer. Conclusion:1 The hOGG1 Cys/Cys and p53 Pro/Pro genotype are associated with susceptibility to lung cancer in China, which suggests that it can be applied to premonish and defend for high risk individual to lung cancer as a biomarker of genetic susceptibility.2 Smoking is a major risk factor to lung cancer, especially for individuals earring hOGG1 Cys/Cys genotype or p53 Pro/Pro genotype. Intevening to smoking behavior of susceptible individual for lung cancer is very important to preventing lung cancer.
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