The Expression Of DNA Adducts DA In Chronic Atrophis Gastritis, Precancerous Lesions And Gastric Cancer And The Relationship With The CYP2E1 Gene Polymorphism

Introduction:Oxidative stress is considered to be one of the important mechanisms of tumor pathogenesis, and it promote formation of active aldehydes by lipid peroxidation, then the complex combined with DNA bases mediated the process of tumor development. Recent research has confirmed the role in the liver, lung and colon tissues.CYP2E1 as an important biological metabolism enzyme, its gene polymorphism was associated with tumor susceptibility, now the relationship between CYPE1 gene polymorphism and the DNA adducts cause much attention.Objective :1. To study the expression of DNA adductsεdA in gastric mucosa tissues to discuss the possible role in chronic atrophic gastritis, gastric precancerous lesions and gas-tric cancer;2. To detect CYP2E1 Rsa I genetic locus and allele frequencies ,then discuss the relationship between gene polymorphism and DNA adductεdA formation.Methods:80 cases were collected from October 2009 to October 2010 at the digestive endoscopy center,Tongji Hospital, Huazhong university of science and technology, of which 39 patients of mild superficial gastritis (control group), 9 cases of chronic atrophic gastritis, 17cases of chronic atrophic gastritis and intestinal metaplasia, and 4 cases of epithelial neoplasia, 11 cases with gastric cancer. The gastric mucosa biopsy were fixed in 10% neutral formalin, After regular dehydration ,transparent, paraffin embedding,slice processing, the expression level of gastric mucosaεdA were detected by immunohistochemical SP method.At the same time patients blood was taked 3ml, after the separation of white blood cells ,its RNA was extracted, RT-PCR and RFLP were used to detect of CYP2E1 Rsa I genetic locus and allele frequency distribution.Results:the positive expression rate of DNA adductsεdA in chronic atrophic gastritis, intestinal metaplasia, intraepithelial neoplasia and tumor group are 77.68%, 76.48%, 75.00% and 81.82%, which were significantly higher than control group 10.36% (P <0.01)CYP2E1 Rsa I genetic locus genotype C1/C2 heterozygous genotype have a high risk of gastric precancerous lesions and gastric cancer than in the pure wild homozygous C1/C1, OR value is 1.38 (95% CI :0.85-2 .35). The effect ofεdA and the C1/C2 of CYP2E1 which were risk factors in the role of gastric malignancy is not independent, there is a causal relationship between the them (P <0.05 OR = 1.89 95% CI (1.05-3.28).Conclusion:1.DNA adductsεdA as a biochemical marker could be detected in the early stage of t-umorigenesis.it may be helpful for gastric cancer and precancerous lesions early screening;2. Mutations Genotype have much more effects than the wild genotype of CYP2E1 in the process of oxidative stress which promote the formation of DNA adducts.It inc- rease the instability of DNA and played an important role in tumor development.