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A Study On The Association Of Chlamydia Pneumonia Infection And Genome-Wide DNA Methylation With Lung Cancer

Posted on:2017-01-02Degree:MasterType:Thesis
Country:ChinaCandidate:T T YuFull Text:PDF
GTID:2334330503473845Subject:Epidemiology and Health Statistics
Abstract/Summary:PDF Full Text Request
[Objective]1?To explore the relationship between the infection of chlamydia pneumonia and prognosis of lung cancer.2?we assess the methylation statue of lung cancer tissue and normal lung tissue with Cpn positive or Cpn negative, to explore altered patterns of DNA methylation associated with Cpn infection of lung cancer, which is thought to contribute to lung cancer risk. [Methods]1?A case-control study was conduted with 298 patients and 362 control subjects. Patients were recruited from the First affiliated hospital and the affiliated Union Hospital of Fujian Medical University and Fuzhou General Hospital with cytological and pathologic confirmation. All healthy controls were enrolled from hospital visitors and community population, and were frequency-matched to the cases on age(±2 year) at diagnosis and gender. Eligible subjects were personally interviewed using a questionnaire. Nurse drawn 5ml peripheral blood before the breakfast of the objects and got serum by centrifugation. Then MIF assay was used to detect the antibodies of Cpn in serum.2?We choosed 6 patients with Cpn positive and 6 patients with Cpn negative. They were frequency-matched on age?gender?pathological type?stage of tumor?smoking and drinking. The lung cancer tissue and normal lung tissue from the 12 patients was obtained and was extracted DNA. DNA was made bisulfite treatment. The Illumina Infinium Human Methylation 450 was performed to detect methylation statue of all samples. We identified altered methylation lever of several genes association with Cpn infection. Cluster analysis and Gene ontology were used to identify the function of the candidate genes.[Results]1?Among control group,the rate of Cpn Ig G-Positive was 51.4% and the rate of Cpn Ig A-Positive was 22.4%.Among case group,the rate of Cpn Ig G-Positive was 68.8% and the rate of Cpn Ig A-Positive was 41.3%. Individuals seropositive for Cpn antibodies had significantly increased the risk of lung cancer. The OR for Cpn Ig G-Positive and Cpn Ig A-Positive were 2.13(95%CI:1.47-3.09) and 2.57(95%CI:1.72-3.82). It showed that the Cpn infection was associated with lung cancer.2?Stratified analysis by age,gender and smoking showed that the Cpn infection was associated with lung cancer in all population groups but females.3?The analysis of combined effects and interactions showed that there was a positive combined effect among smoking ?indoor and outdoor air pollution and Cpn Ig G/Ig A antibodies.4?We compared the global DNA methylation pattern between lung cancer tissue and normal lung cancer from the patients with Cpn positive to discover 2349 differentially methylated genes, including 1525 hypermethylated and 824 hypomethylated differentially methylated genes.We also compared the global DNA methylation pattern between lung cancer tissue and normal lung cancer from the patients with Cpn negative to discover 2622 differentially methylated genes, including 1570 hypermethylated and 1052 hypomethylated differentially methylated genes.5?By comparing the two sets of results, we obtained 73 Cpn-induced DNA methylations specific to lung cancer, including 37 hypermethylated and 36 hypomethylated differentially methylated genes. The 73 differentially methylated genes were mostly enriched in biological processes andmolecular function. [Conclusion]1?Cpn infection not only was an independent risk factor of lung cancer, but also may act synergistically with smoking and indoor and outdoor air pollution for lung cancer.2?Cpn infection may play an important role in the development of lung cancer through DNA methylation.
Keywords/Search Tags:Lung cancer, Chlamydia pneumonia(Cpn), genome-wide, DNA methylation
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