The Relationship Between The Deletion Of GSTM1, GSTT1 And Susceptibility To Lung Cancer

Lung cancer is a common malignant tumor; its increasing rate is very quickly. The carcinogenesis is related to not only environmental exposure but also individual genetic diathesis such as the polymorphisms of genes.Glutamione S transferases are multifunctional enzymes that catalyse the conjugation of glutathione (GSH) to a variety of electrophiles such as arene oxides, unsaturated carbonyls, organic halids and other substrates to decrease their toxicity or increase their hydrophile, thereby strengthen the elimination of these harmful compounds and protect macromolecules. In human eight distinct gene families encode these soluble GSTs, including alpha , mu ,theta, pi, zeta,sigma, kappa and chi (also called omega). So far, the polymorphisms of many members of the family have been studied, while most studies were focused on mu and theta class.GSTM1 , GSTTI is a member of mu and theta class, respectively. GSTM1 has three kinds of allele variants, namely GSTM1*0, GSTM1*A and GSTM1*B. GSTTI also has the polymorphic genotype of null homozygote. Initial studies reported lung cancer was correlated with GSTM1 null genotype. Since then there have been many studies though conflicting data have been obtained and the influence of GSTM1 on cancer risk remains unclear. In our country though there have been many studiesabout GSTM1 , GSTT1 polymorphisms and susceptibility to Chinese patients with lung cancer, the results were also inconsistent.We detected the frequency of GSTM1 ,GSTT1 null genotype in patients with lung cancer in Henan province by PCR and the expression of P16 protein in lung cancer tissues using SDS-PAGE and Western blot to discuss the association between the polymorphism of GSTM1 -. GSTT1 and lung cancer and its possible mechanism in order to provide an evidence for GSTM1 and GSTT1 being used in studying the etiology of lung cancer and cancer prevention. Materials and methods:1. Collect samples: Seventy-seven tissue samples were collected from cases with lung cancer, which were used for analyzing genotypes of the two genes. And among them there were fifty-six samples used for analyzing both genes and protein. Meanwhile 107 whole blood samples of healthy people were collected as controls.2. Analyse the genotype of the target genes using PCR.3. Detect the expression of P16 protein in normal tissues using SDS-PAGE and Western-blot.4. Process the data using chi-square test and nonparametric test of SPSS 10.0. Results:1. The result of GSTM1 after PCR:By PCR we detected 45 lung cancer patients with GSTM1 null genotype, that was 58.4% in all cases; and there were 45 individuals (42.1%) with GSTM1 null genotype in controls. There was significant difference between the two groups (P<0.05) and its OR was 1.938 (95%CI 1.095-3.581). But there was no difference of GSTM1 null genotype in different render and histological tissues (P>0.05).2. The result of GSTT1 after PCR:By PCR we found 44 lung cancer patients with GSTT1 null genotype, that was 57.1% in all cases; and there were 54 individuals (50.5%) with GSTT1 null genotype in controls. There was significant difference between the two groups (P<0.05) and its OR was 1.270 (95%CI 0.707-2.283). And there was no difference of GSTT1 null genotype in different render and histological tissues either (P>0.05).3. The influence of GSTM1/GSTT1 combined genotypes on susceptibility to lung cancer:There were 26 cases with GSTM1 null/GSTTl null genotype in patients which was significantly higher than those in controls, its OR was 2.451 (95%CI 1.067-5.633) ; and there wasn't significant difference between cases and controls for GSTM1 null/GSTTl non-null and GSTM1 non-null /GSTTI null genotypes. 4. The level of P1 6 protein:There was significant difference about the levels of P1 6 protein between individuals with GSTM1 null genotype and those with GSTM1 non-null genotype as well as the group of GSTM1 /GSTTI combined null genotype and those of GSTM1/GSTT1 combined positive (P<0.05). Conclusion:1. The frequency of GSTM1...