A Study On Relationship Between Genetic Polymorphism Of GSTM1 And GSTT1 Gene And Susceptibility To Lung Cancer In The Population Of Northern Sichuan Of China

Lung cancer is one of the common malignant tumor which is the leading cause of malignant tumor death among global male people. Epidemiological studies have demonstrated that smoking, environmental and genetic factors and other factors plays an important role in the development of lung cancer.Glutathione s-transferase (GST) is a phase II enzymes, its main function is to catalyze reaction of combine between the pro-electronic products of the phase I enzyme metabolism and glutathione,which become water-soluble substances discharged from the body and its DNA Toxicity was eliminated. Human GST gene is a supergene family, including four subfamilies: Alpha (A), Mu (M), Theat (T) and Pi (P). The Glutathione S-transferase M1(GSTM1) main catalyst covalent binding between glutathione and hydroxyl metabolite of epoxide and benzopyrene and other tobacco-related carcinogens to detoxifying. The Glutathione S-transferase T1 (GSTT1) was related to biological transformation of some of the major low molecular weight toxins (such as ethylene oxide, butadiene and other components of these tobacco). GSTM1 and GSTT1 genes were studied most in GST supergene family. GSTM1 and GSTT1 both have genotype of homozygous deletion of alleles. GSTM1 null genotype was first closely reported related to susceptibility of lung cancer in 1990, then many studies(including studies in China) were reported but the results were inconsistent. The relation between GSTM1 and GSTT1 and susceptibility of lung cancer remains unclear. Although many studies suggest GSTM1and GSTT1 genotype were related to susceptibility of lung cancer, but there are differences in ethnic groups, and its exact mechanism is unknown.This study use polymerase chain reaction technique (PCR) to detect the frequency of GSTM1 and GSTT1 null genotype in lung cancer and healthy controls to explore the relationship between the Genetic polymorphism of GSTM1 and GSTT1 gene and Susceptibility to lung cancer in the population of North Sichuan of China.It may be provide a theoretical evidence to prevention and early diagnosis of lung cancer. Methods: The case-control study was conducted among 125 lung cancer and 125 healthy controls of northern region of Sichuan Province in China. The genotypes of GSTM1 and GSTT1 were detected by PCR to analyze the relationship between the genetic polymorphism of GSTM1 and GSTT1 gene and smoking and the susceptibility to lung cancer.Results:1,GSTM1 (-) and lung cancer susceptibilityGSTM1 (-) genotype were 73 cases and 71 cases in lung cancer and healthy controls respectively and the frequency were 58.4% and 56.8% respectively. The frequency of GSTM1(-) in both groups did not have significant difference by chi-square test (χ~2 = 0.066, P=0.789). There were no significant difference in different histological types and sex (P>0.05). By stratified analysis, GSTM1(-) genotype associated with decreased risk of lung cancer compared with GSTM1(+) genotype (OR=0.793, 95%CI=0.369-1.704) in smokers and associated with increased risk of lung cancer compared with GSTM1(+) genotype(OR=1.428, 95%CI=0.700-2.912) in no smokers. But there was no significant difference(P>0.05). 2,GSTT1 (-) and lung cancer susceptibilityGSTT1 (-) genotype were 56 cases and 56 cases in lung cancer and healthy controls respectively and the frequency were 45.6% and 44.8% respectively. The frequency of GSTT1 (-) in both groups did not have significant difference by chi-square test (χ2=0.016,P=0.899).There were no significant difference in different histological types and sex (P>0.05). By stratified analysis, GSTT1(-) genotype associated with decreased risk of lung cancer compared with GSTT1(+) genotype (OR=0.969, 95%CI=0.451-2.081) in smokers and associated with increased risk of lung cancer compared with GSTT1(+) genotype(OR=1.251, 95%CI=0.624-2.508) in no smokers. But there was no significant difference(P>0.05).3,The combine of GSTM1/GSTT1 on susceptibility to lung cancerThe frequency of combined genotypes GSTM1(-)/GSTT1(-) was 28.8%(36/125)in lung cancer and slightly higher than that of 24.0%(30/125)in healthy controls. Compared with GSTM1(+)/GSTT1(+) genotype carriers,the estimated relative risk forGSTM1(-)/GSTT1(-) genotype carriers was no significant difference (OR=1.084,95% CI=0.536-2.192,P=0.823) by Logistic regression analysis and no interaction with smoking. In addition smoking clearly increase risk of lung cancer in Northern region of Sichuan Province (OR=2.68,95% CI=1.604-4.469, P=0.000).Conclusion:1. No significant interaction was observed between GSTM1 null genotype and susceptibility of lung cancer. There were no significant difference in different histological types and sex (P>0.05). There may be a synergetic interaction between smoking and GSTM1(-) genotype. 2. No significant interaction was observed between GSTT1 null genotype and susceptibility of lung cancer. There were no significant difference in different histological types and sex (P>0.05). There may be a synergetic interaction between smoking and GSTT1(-) genotype.3. Genotype combined GSTM1(-)/GSTT1(-) does not increase the risk of lung cancer.4. Smoking clearly increases the risk of lung cancer.