A Study For The Development Of Lung Cancer And Chronic Obstructive Pulmonary Disease Related To The GSTM1 Gene Polymorphisms And Oxidative Stress

Lung cancer (LC) is a common malignant disease with the highest incidence in the human being and the most common cause of death from cancer in many countries. Although chronic obstructive pulmonary disease (COPD) is a benign lesion of the lung, however it frequently occurs with the lung cancer coincidently and lowers the opportunity of surgical treatment of LC due to its poor pulmonary function. To investigate whether the GSTM1 gene polymorphisms and oxidative stress are related to the development of COPD and LC, a hospital-based case-control study and the techniques of molecular biology and immunology including PCR, ELISA, hybrid tumor mono-cloning antibody were taken to detect the interaction of the gene polymorphisms, environmental risk factors such as tobacco smoking, history of cancer or COPD, and oxidative stress in the development of both COPD and LC in this study. The all data and findings of this study were analyzed by Chi square test, mono and multiple variables logistic regression model. The dose response models of gene environmental interaction, ORe, ORg, OReg and their 95% confidence intervals were created. The results showed thatA. The major environmental and genetic risk factors in the development of LC arid COPD are cigarette smoking and history of COPD which played a very important interactive role in the development of the two diseases with interaction OReg value 4.990 and 4.589 respectively. It was confirmed to be an excess multiplicative model. It was also found that tobacco smoking andLC family history acted a multiplicative interaction role in the development of LC with OReg value 4.042.B. An interaction of GSTM1 null genotype and cigarette smoking with dose response LEG model exited in the development of lung cancer, which meant a stronger interaction might be present at the stage of small amount of smoking and the interaction would be weaken down while the volume of smoking increased owing to the enzyme promoting dose response reaction.C. There was no evidence to prove that GSTM1 null genotype being closely related to the development of COPD and staging of LC pathologically and clinically.D. The concentration of 8-isoprostane in group COPD (154.26+43.58 pg/ml )and LC (112.47+25.31 pg/ml) were significantly higher than that in the group control (85.78 + 13.47 pg/ml ). It indicated that the lung tissue of patients with COPD or LC was injured much severer by oxidative stress than those without COPD or lung neoplasm.E. Comparing the concentration of 8-isoprostane in the experimental groups with control, it was remarkably higher in the group COPD with OR value 2.46 that doubled the limitation, but there was no significant difference between group COPD and LC. It implicated that the oxidative stress was closely related to the development of COPD other than LC.F. Both concentration of 8-isoprostane and rate of GSTM1 null genotype in the group CODP and LC were significantly higher than those in the control group. It indicated that GSTM1 gene might minimize the injury of the tissue from the oxidative stress.Conclusion: GSTM1 gene polymorphisms are genes those might be very important and susceptible to the development of lung cancer and closely interacted with cigarette smoking. The oxidative stress was one of the main causes to the development of COPD. GSTM1 gene may be able to prevent the damage from oxidative stress. Based on the results, we believe that this study would provide a theoretical evidence to see the insight of the molecular mechanisms of development of lung cancer and COPD and to instruct primary prevention of higher risk population.