Association Of Genetic Polymorphisms In The Promoter Region Of TNF-A,IL-1B And IL-10 With The Susceptibility To Chronic Obstructive Pulmonary Disease And Lung Cancer

Chronic obstructive pulmonary disease(COPD) is a common pulmonary disease,with the increasing prevalence of morbility and mortality.Among the population above 40 years old,the morbility has been up to 8.2%.Lung cancer is a pulmonary malignant tumor with high mortality and is the first leading cause of death in some regions.Epidemiology studies confirm that COPD is a high risk for developing into lung cancer.The rate of occurrence of lung carcinogenesis increases with decreasing lung function.Therefore,active measures should be taken to prevent the prevalence of COPD and lung cancer.Currently available early detection options are based on the occurrence of pathologic and physiologic abnormality and have limited value in evaluating the onset risk for COPD or lung cancer.With the development of molecular epidemiology, researches using single nucleotide polymorphisms(SNPs) as a biomarker of disease onset are becoming hot spot.Both COPD and lung cancer are associated with cigarette smoking.However,only 10-20% and 10-15%of cigarette smokers will eventually develop into clinically significant COPD and lung cancer.These results support the hypothesis that genetic factors are involved in the pathogenesis of COPD and lung cancer.Moreover,COPD is considered to be at increased risk for lung carcinogenesis,the reason of which is still unknown.In this study,we conducted the technique and the theory of molecular epidemiology and performed for the first time in Chinese population a case-control study researching for the association of genetic polymorphisms of three genes(TNF-α,IL-βand IL-10) with the susceptibility to COPD and lung cancer,as well as the interaction between gene and environment using cigarette smoking as an environmental exposure. In our results,we show that:(1) IL-1β-511 is not only associated with the susceptibility to COPD in male population,but also the severity of COPD.Furthermore,there is a gene-environment interaction between IL-1β-511 and smoking.(2) The genetic polymorphisms of TNF-α-308 and IL-1β-511 are associated with the susceptibility to lung cancer in non-smoker population and there may be a gene-environment interaction between the two SNPs and smoking.(3) IL-1β-511 T/T genotype is associated with the susceptibility to simple COPD and COPD merged with lung cancer in smoker population.Besides,the odds ratio for developing to COPD merged with lung cancer is higher than that for developing to simple COPD.In conclusion,TNF-α-308 could be identified as a candidate biomarker for early diagnosis of lung cancer;and IL-1β-511 could be identified as a candidate biomarker for early detection of COPD and lung cancer;and IL- 1β-511 T/T may play an important role in COPD developing into lung cancer.