Polymorphism Of CYP1A1 Gene And Methylation Of Tumor Suppressor Genes In Plasma Related With Lung Cancer

Objective To study the relationship among the genetic polymorphism of CYP1A1 gene, the methylation of p16,MGMT,DAPK,RARβand TIMP-3 genes and the susceptibility to lung cancer, and to explore the mechanism of lung cancer and offer an effective means for the earlier diagnosis of the malignancy.Methods A case-control study was conducted among 150 cases of lung cancer and 454 healthy controls,the data of environment exposure were collected by uniform questionnaire, the genetic polymorphisms of CYP1A1 gene were genotyped with the method of PCR-RFLP, the methylation of tumor suppressor genes were detected by MS-pcr technique.Results There was a statistical correlation between smoking and lung cancer(P<0.05), there was a statistical significance between SCC and smoking with a strata study, there seems no statistical significance between AC and smoking. There was a high frequency of dust and toxicant exposure in cases than that in controls (P<0.01); The frequency of eating vegetables, fruits and drinking sanitized water was lower in cases(P<0.01). The distribution of CYP1A1 genotypes recognized by MspI found no statistical significance between cases and controls (P>0.05), and it's also not seen in the histological types in lung cancer. There was a low-grade synergistic interaction among dust exposure,tobacco exposure and CYP1A1 B genotype. There may be no independant effect between CYP1A1 genetypes and the susceptiblity of lung cancer in this area. Hypermethylation for p16,MGMT,DAPK,RARβand TIMP-3 gene promoters were 30.7%,18.0%,20.0%,26.0% and 12.0%,141 cases (94%) can be detected that at least one gene was methylated among five tumor suppresor genes in plasma of lung cancer patients. whereas no methylated p16,MGMT,DAPK,RARβand TIMP-3 gene promoters were found in plasma from the normal controls(P<0.01). Methylated promoters of five genes in plasma were not closely correlated with the pathological classification and TNM stage in lung cancer(P>0.05). Methylation of p16,DAPK and RARbeta genes in plasma significantly correlated with smoking(P<0.05). Methylation of five genes did not correlate with polymorphism of CYP1A1 gene.Conclusions Smoking, dust, and toxicant exposure significantly increased the risk of lung cancer, intaking vegetables, fruits, and sanitized water frequently decreased the risk of lung cancer, there was a low-grade synergistic interaction between the tobacco exposure and CYP1A1 B genotype. There may be no independent effect in CYP1A1 gene with the susceptiblity of lung cancer in this area. This study revealed that detection of the aberrant methylation of tumor suppresor genes in plasma DNA from lung cancer patients by MSP method might offer an effective means for the earlier diagnosis of the malignancy.