Genetic Polymorphism In HOGG1 And Susceptibility To Chronic Atrophic Gastritis, Gastric Cancer

Chronic Atrophic Gastritis(CAG) is a common disease in clinic .Because of its positive correlation with morbidity of gastric carcinoma.It was considered as precancerous condition by World Health Organization(WHO). Gastric cancer is the second most common fatal malignancy in the world. It causes more than 750 000 deaths annually. The survival rate is very poor, usually less than 15% at five years. Reactive oxygen species have also been demonstrated to play a crucial role in the pathophysiology of CAG and gastric cancer. 8-OH-dG is a product and bio-marker of oxidative DNA damage, The hOGG1 gene encodes a DNA glycosylase that excises 8-OH-dG from damaged DNA.To examine the association between Ser326Cys polymorphism in HOGG1 gene , which is involved in the repair of 8-hydroxyguanine in damaged DNA,and investigate the risk of CAG and gastric cancer.Materials and MethodsSer326Cys polymorphism in HOGG1 gene was detemined by PCR-RFLP among 21 gastric cancer patients,26 CAG patients and 29 normal controls . Blood was collected before surgical treatment and chemotherapy. The association between this genetic polymorphism and the risk of the cancer and CAG was examined by amultivariate analysis. The association between the HOGG1 polymorphism and CAG, cancer risk was estimated by the odds ratio (OR).ResultsThere were no significant statistical differences in age between the case and control groups. Three banding patterns were observed depending on the genotypes; a single 293bp band corresponding to the Ser326/Ser326 genotype, a 293, 124 and 169 bp bands that corresponded to the Ser326/Cys326 genotype, and 124 and 169bp bands corresponding to the 326Cys/Cys326 genotype.We did not observe any correlation between the Serl245Cys polymorphism of the hOGG1 gene and gastric cancer. Therefore, other polymorphisms of DNA repair genes or/and environmental factors, including H. pylori, smoking and diet, may contribute to gastric cancer.Although the sample size was limited ,these result suggest that somatic mutation or the polymorphism of HOGG1 is less likely to be involved in gastric cancer.The Cys/Cys genotype of hogg1 was found in 42.3% of patients with CAG and 17.2% of the controls (P<0.05) .Homozygosity for the Cys/Cys genotype significantly increased the risk of developing cancer,with the odds rate being 3.52(95% CI=1.020～12.145)Conclution1. Polymorphism of HOGG1 Ser326Cys may play a role in CAG.2.These results suggest that the hOGG1 Ser326Cys polymorphism is probably not amajor contributor to individual gastric cancer susceptibility overall.