Polymorphism Of GSTM1 And Methylation Of P16/DAPK Related With Susceptibility To Non-Small Cell Lung Cancer

Objective To study the relationship among the genetic polymorphism of GSTM1 gene, methylation of P16 and DAPK gene, environment exposure and susceptibility to non- small cell lung cancer so as to explore the mechanism of lung cancer and perfect the theory of diagnosis, prevention and therapy for non- small cell lung cancer.Methods The case-control study was conducted among 94 non- small cell lung cancer cases and 94 healthy controls, data of environment exposure were collected by uniform questionnaire, the GSTM1 gene genetic polymorphisms in peripheral blood DNA were genotyped with the method of PCR-RFLP, methylation of p16 gene was tested in DNA from 94 lung cancer tissues and adjacent nomalignant tissues by MSP technique.Results The NSCLC patients were more seen in worker and peasant groups, there was a statistical correlation in smoking and NSCLC(P<0.05), there was a high frequency of dust and toxicant exposure in cases than in controls (P<0.01), the same in deep-fry fats eating(P<0.01), by contrary, frequency of eating vegetables, fruits and drinking sanitized water frequently was lower in cases(P<0.01). There was no statistical difference of GSTM1 null genotype frequency between case and control (P>0.05), there was a low-grade synergistic interaction between dust , poison and tobacco exposure with GSTM1 null genotype. The methylation frequency of P16 and DAPK was 41.5% and 50% in tumour tissues, significantly higher than that in the nomalignant tissue 10.6%and 16%(P<0.01), methylation of P16 and DAPK significantly correlated with smoking (P<0.01), methylation of P16 was more seen in squamous cell carcinoma, methylation of P16 and DAPK did not correlate with polymorphism of GSTM1.Conclusion This study revealed there was some correlation beween NSCLC and occupation, smoking, dust, toxicant exposure and deep-fry fats eating significantly increase the risk of non- small cell lung cancer, consumption of vegetables, fruits, and sanitized water frequently was associated with the decreased risk of lung cancer. There was no obvious effect in GSTM1 null genotype alone with lung cancer, maybe there was an elevated risk of lung cancer in GSTM1 null genotype with exposure to smoking, dust and tobacco. Methylation of P16 and DAPK gene owing to smoking was involved in the progress of non- small cell lung cancer, there was tissue specificity in methylation of P16 gene, this study did not reveal the interaction between polymorphism of GSTM1 and methylation of P16 in lung cancer.