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Relationship Between Genetype Of GSTM1 Gene And K-ras Gene Mutation In Patients With Lung Cancer

Posted on:2008-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:X G HuFull Text:PDF
GTID:2144360215960515Subject:Respiratory medicine
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Background and ObjectiveWe use the method of retrospective case-control study in Henan Chinese people to study the relationship between the genetype of smoking ,GSTM1 gene and K-ras gene mutation in lung cancer,and the correlation between the genetype of GSTM1 genetype and K-ras gene mutation.To discuss the mechanism of lung cancer susceptibility in group of GSTM1 deletion , in order to find its value for early diagnosis,prognosis assessment of lung cancer and design for new treatement strategy.Materials and methodsTo analyze the polymorphisms of GSTM1 and K-ras mutations in specimen,we use the method of polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism (RFLP).Cases in two groups were recruited from the patients who received bronchoscope examination in bronchoscopic room of first and second affiliated hospital of Zhengzhou university from November in 2005 to May in 2006.A11 cases were received pathologic check in the form of bronchofibroscope biopsy or brush biopsy or cast-off cells in BALF.The experimental group includs 112 cases of lung cancer patients,which were histopathologically confirmed to be primary bronchogenic carcinoma for the first time exclude other simultaneous malignancies.Control group includes 104 subjects with matched age and sex frequencies who were histopathologically confirmed to be benign diseases.Ail of the recruits were questionnaire investigated to ascertain his diseases and to exclude tumours.ResultsThe allele frequencies of GSTM1 deletion were 55.8% and 67.9% in control and experimental group,the proportion of experimental group is much higher than control group,which showed statistically significantly difference.The adjusted OR of the GSTM1 deletion genotype showed a 1.652 fold increased risk for lung cancer, respectively, when compared with the other genotypes. The mutation rate of K-ras in lung cancer and benign diseases was 42.9% and 2.9% respectively. Smokers showed a 3.156 fold increased risk for lung cancer when compared with those unsmokers.The K-ras mutation rate was 60.5% in group of GSTM1 deletion and 19.4% in group of nomal GSTM1 gene respectively.There was a significant difference between the two groups.Conclusions(1).GSTM1 deletion gene is the susceptible factor of lung cancer.GSTM1 deletion have the synergistic effect with smoking to increase the risk of lung cancer.(2).Smoking is one of the important factors which caused K-ras oncogene mutation, while K-ras gene is one of the target gene of tabacco carcinogen.(3).Detection of K-ras oncogene mutation in BALF might to be useful in early diagnosis of lung cancer, which improves the diagnostic yields of fiberbronchoscopy of peripheral lung cancer,especially in patients with adenocarcinoma.(4).The cause of K-ras gene mutation in the group with GSTM1 deletion gene type who suffer from lung cancer may be in part an accumulation on BP diol epoxide which is not well detoxified .However, further study should be made to find out the inner ralation between them.
Keywords/Search Tags:Lung cancer, Bronchoalveolar lavage fluid, GSTM1, Genetic polymorphism, K-ras gene, Mutation, Genetic susceptibility
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