The Signification And Relationship Between GSTP1 Genotypes And Precancerous Lesions Of Gastric Cancer

PrefaceGastric cancer is one of the malignant carcinoma harmful to human health. The mortality of gastric cancer is the highest in all kinds of cancer in China. Many research show that the carcerization of gastric mucosa is a more factors and more steps process. The cause of gastric cancer is not clear, so it is difficulty to preventive first by controlling the causes . Most people focus on the research the precancerous of gastric cancer ----intestinal metaplasia (IM)and dysplasia (GD)in epidemiology , pathology , microbiology different sides .The result show that 40%-100% postoperative specimen of early gastric cancer can be observed dysplasia , 5%-80% specimen of progress gastric cancer can be found various degree dysplasia.83.4% IM can be found in the mucosa around the gastric cancer ,and the IM and GD are very resemble to the gastric cancer in the morphology ,biological behavior and the change of biological marks such as tumor antigens ,enzymes ,and some gene (p53,p16,p21,ras). At the same time ,people also find that not all the precancerous lesion would develop to gastric cancer .They divided the IM and GD in different kinds and grade ,and found the relationship were different with gastric cancer .IM III and severe grade GD have close relationship with gastric cancer ,but also not all of the IM III and severe grade GD would develop to gastric cancer .So how to distinguish the true precancerous lesion is very important .The gene polymorphism is one of the material bases of the individual susceptibly to carcinoma ,so detection the gene polymorphism is a good method to make sure the high-risk people of cancer .There many gene polymorphism are relative to gastric cancer , among them the metabolic enzyme are important one .GSTs is the II enzyme in human body ,GST-πis one of GSTs and has close relationship with gastric caner .The gene of GST-π(GSTP1)has two site polymorphism ,one is location in 1587 bp of 5 exon A-G, the amino acid change from Ile to Val , the other is location in 2293bp of 6 exon C-G, the amino acid change from Ala to Val .The polymorphism of GSTP1 has relationship with breast cancer ,oval carcinoma ,large intestinal carcinoma ,cervix carcinoma , COPD and so on ,especially the polymorphism of 5exon .In Northeast of China reported that the individuals with GSTP1 Val allele gene show an increased risk of gastric caner .On the basic of the research ,we will detect the polymorphism of GSTP1 on the 5 exon in IM and GD group using PCR-RFLP method, to grasp the regular rule of polymorphism in people of IM and GD, and different kinds and grades of IM and GD ,in order to distinguish the precancerous lesions of gastric cancer .Material and MethodsThe pathological diagnose and degree of GD are used the H.E stain . The subtypes of IM are classified by high-iron diamine /alcian blue pH2.5/periodic acid–Schiff (HID-ABpH 2.5-PAS) method. H.pylori infection was confirmed or excluded in all patients by histological examination hematoxylin-eosin (HE), and enzyme-linked immunosorbent assay(ELISA) for anti- H.pylori immunoglobulin G(IgG). The polymorphism of GSTP1 were determined by PCR-RFLP method.The subjects in present study ,whose sample including serum ,sludged blood and gastric mucosa collected from the first Affiliated Hospital of China Medical University for gastroscopy .Including 50 normal mucosa ,50 IM,50GD,and 50 gastric cancer, male 108cases ,female 92cases ,mean age 51±10.80.Information about gender ,age and other factors was obtained by means of a questionnaire administered to each subject .The study protocols were approved by the Human Ethics Review Committee of China Medical University .The X2 test or Fisher's Exact Test were used to examine the differences in the different groups .The medians of variables were compared between two groups by the Mann-Whitney U tests .The Odds ration (ORs)and their 95% confidence interval were calculated by unconditional logistic models .An interaction was assessed by crossover analysis ;synergy index and attributable proportion of interaction were calculated .Results1 The relationship between the different lesions and polymorphism of GSTP1In the normal gastric mucosa group the main genotype is A/A type ,the allele frequencies of A is higher than the group of IM, GD and gastric cancer group ; and there are no static signification of A allele frequencies between the group of IM ,GD and gastric cancer .The allele frequencies of A is decreased ,and the allele frequencies of G is increased from normal gastric mucosa→IM→GD→gastric cancer group.2 The relationship between the different types IM and polymorphism of GSTP1The allele frequencies of A in III IM is lower than II and I type IM and normal group (P <0.01) , The allele frequencies of A is decreased ,and the allele frequencies of G is increased from normal gastric mucosa→IM I,II→IM III→gastric cancer group.3 The relationship between the different grade of GD and polymorphism of GSTP1The allele frequencies of A in sever GD is lower than slight and middle degree of GD and normal group (P <0.01) , The allele frequencies of A is decreased ,and the allele frequencies of G is increased from normal gastric mucosa→slight and middle degree of GD→sever GD→gastric cancer group.Conclusion1 The IM and GD with allele A of GSTP1 has high risk to develop gastric cancer.2 The III IM with allele G of GSTP1close relationship with gastric cancer ,and the risk of development gastric cancer is higher than I and II IM. The severe type GD with allele of has close relationship with gastric cancer ,and the risk of development gastric cancer is higher than slight and middle degree of GD3 The III IM or severe type GD allele G of GSTP1can be regarded as precancerous lesion ,which should be cure and followed up.