| Objective To investigate the correlation between gene hypermethylation of multiple tumor suppressor genes in CpG islands of promoter and lung cancer. Methods Using methods of case-only study,collect the environmental epidemiological datas of 200 primary lung cancer patients,take the primary lung cancer tissues and corresponding nonmalignant lung tissues.Methylation-specific PCR were used to detect the promoter methylation of the tumor suppressor genes, and I analyze the data by chi-square test and logistic regression analysis. Results Methylation in the tumor tissues was detected in 51.0% for p16,60.0% for DAPK,58.0% for RARβ,16.5% for MGMT and 28.0% for TIMP-3,whereas with significant difference (P<0.01)between which in the corresponding nonmalignant tissues respectively(12.5% for p16,11.5% for DAPK,15.0% for RARβ,2.0% for MGMT and 10.0% for TIMP-3).90.5% of lung cancer tissues had methylation in more than one tumor suppressor gene,more than that in corresponding nonmalignant tissues which was 34.5%(P<0.01).Tumor suppressor genes methylation in tumor tissues was associated with age,gender,histologic type,TNM stage and anatomic sites. The methylation of DAPK gene increased the risk of p16 and MGMT gene methylation with OR of 1.95(P<0.01) and 4.03(P<0.01).The RARβgene methylation increased the risk of TIMP-3 gene methylation by OR of 2.16(P<0.05).It imply that DAPK gene methylation was associated with p16 and MGMT gene methylation, RARβgene methylation related with TIMP-3 gene methylation in tumorigenesis and development of lung cancer.Smoking increased the risk of p16 and DAPK methylation in lung cancer patients; by OR of 3.07 (P<0.05) and 3.49(P<0.05).Conclusion The tumor suppressor gene methylation play an important role in development of lung cancer and are strongly associated with clinical data of lung cancer. Somking of lung cancer patients increased the risk of methylation of tumor suppressor genes.
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