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The Association Between Inflammatory Gene Polymorphisms, Environmental Factors And Chlamydia Pneumonia Infection And The Susceptibility And Prognosis Of Lung Cancer

Posted on:2014-02-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:F HeFull Text:PDF
GTID:1224330392967114Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
[Objective]To investigate the main impact environment factors of lung cancer and theindependent and interaction effects of polymorphisms of inflammatory genes andenvironmental facts on the development and prognosis of lung cancer in Han Chinesein southeast China; to explore the relationship between the expression of miR-155andprognosis of lung cancer.[Methods]1. A case-control design was applied in this study. A total of1300patients oflung cancer diagnosed with histology and1547control subjects consisted of hospitalvisitors and community population were enrolled. Eligible subjects were personallyinterviewed using a questionnaire about personal customs. Using SAS9.2,buildinggeneral linear model to evaluate the influence factors of lung cancer separately thesmokers and non-smokers.2.5ml non-anticoagulative blood samples were collected from each participatesto detect chlamydia pneumonia and explore the association between Cpn and lungcancer.3. Desiging molecular epidemiology study,5ml peripheral blood of each caseand saliva for each control were collected and their DNAs were extracted. Predictingthe single nucleotide polymorphisms (SNPs) by biological softs and these25SNPswere genotyped by SNaPshot. Best genetic models were evaluated by MAX and therelationship between SNPs and lung cancer, the interaction effects of SNPs andenviorment factors were analysed by using SAS9.2.4. All patients were followed prospectively every3monthsfrom the time ofenrollment by patient or family contacts until death. Gather the informations of1165patients to observe the prognosis impact of25SNPs in lung cancer.5. Using Meta analysis and searching database, heterogeneity, publication bias,overall HR and95%CI were explored by Stata12.0. [Results]1. In the somkers, the risk factors were contamination near residential area,living in the bungalow, insufficient ventilation, cooking oil fume, smoke over40pack-year, the history of pulmonary inflammatory dieases, the family history of lungcancer, the fewer fruit intake and with negative character; in the non-smokers, the riskfactors were contamination near residential area, living in the bungalow, insufficientventilation, ETS index over10per year, eat faster than10minutes, cooking oil fume,nerver using vitamin, the fewer fruit intake, the history of pulmonary inflammatorydieases and the family history of lung cancer and the protect factor is drinking tea.2. The positive correlation was exsited in the Chlamydia pneumoniae IgG andIgA (r=0.46); The Cpn IgG positive and IgA positive were related with lung cancer(OR=2.72and4.69). Synergistic effect of Cpn IgG, IgA and smoking, environmentaltobacco smoke and the family history of lung cacner were assocatied with lungcancer.3. In the smoker, rs16900627GG+GA was associated with the risk oflung adenosquamous carcinoma (OR=1.37); IL6R rs4072391T was associated withthe risk of lung adenocarcinoma (OR=1.30); in the non-smokers, STAT6rs703817maybe reduce the risk of lung squamous carcinoma and TLR4rs11536889CC or CGwas the risk factor of lung adenocarcinoma.4. The factors of surgery, clinical stages, gender and the combined effect of TLR4rs11536889, NFKBIA rs2273650and IL-1A rs1304037were the predict impact factorsof lung cancer.5. The high expression of miR-155can predict the poor outcomes of lung cancer.[Conclusion]1. The related inflammatory factors, environment pollution, active and passivesmoking, the history of pulmonary inflammatory dieases and the family history oflung cancerwere identified as the risk factors of lung cancer in Chinese Hanpopulation.2. Chlamydia pneumonia was related with lung cancer.3. The SNPs of RIPK2rs16900627, IL6R rs4072391, STAT6rs703817and TLR4rs11536889were associated with the susceptibility of lung cancer.4. TLR4rs11536889, NFKBIA rs2273650and IL-1A rs1304037can be the predictor of lung cancer.5. Overexpression of miR-155may cause the poor outcome of non-small celllung cancer.
Keywords/Search Tags:lung cancer, inflammation, polymorphisms, susceptibility, prognosis, interaction, chlamydia pneumonia, miRNA-155
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