Population-based Study On The Relationship Between Interleukin-10-1082A/G SNP And The Risk Of Gastric Cancer In North China

PerfaceGastric carcinoma (GC) is a disease seriously threatens peopled health, in which Environmental and host - related factors interact. Environmental factors such as Helicobacter pylori infection persistently act on gastric mucosa which lead to chronic inflammation, host factors e. g. inflammation and anti - inflammatory factors play a crucial role during malignant transformation, which influence severity and progression of gastric mucosa inflammation. The difference a-mong quantities and types of Inflammation factors released such as cytokine and chemotatic factor in different host rely on the polymorphisms in the regions of genes or around of it, which determine susceptibility of gastric diseases. Recently, the studies on susceptibility of host to develop stomach cancer carried out widely in home and abroad, and researchers were attracked by interleukin -10(IL-10) as a antiinflammatory cytokine among multitude cytokines. There are three polymorphims at promoter regions of IL - 10 gene, - 1082G/A (rsl800896) , - 819C/T( rsl800871) , - 592C/A ( rsl800872 ) respectively, which may influence the expression of IL -10 gene. The studies on relationship between IL - 10 — 1082 polymorphism and host susceptivity of stomach cancer have been reported from labs around the world, but conclusions are not completely coincident, and sometimes there are adverse opinions. In this study, we conducted a population - based case control study to investigate the association between IL — 10 - G1082A polymorphism and the risk of gastric cancer, and combined with Helicobacter pylori infection to discuss whether there is synergism between IL - 10 - G1082A SNP and HP infection to the promotion of gastric cancer.Materials and MethodsThe study included 1517 patients came from census population, patients receipt gastroscopy in central hospital of Zhuanghe and patients receipt gastroscopy or surgery in the First Hospital of China Medical University. Venous blood were collected and put in - 20^ chest freezer after serum and blood clot were isolated. Pathologic diagnosis was carried out on the basis of 4 masses of biopsy or resection specimens. The patients were divided into 5 groups as normal, superficial gastritis, gastric ulcer and anabrosis, atrophic gastritis and gastric cancer according to results of pathologic diagnosis. ELISA was carried out to detect H. Pylori Ig — G antibody of serum, consider masculine when tite ^42EIU. Ge-nomic DNA was extracted from blood clot using the method of classic phenol -chloroform, then conserve at -20t chest freezer. IL -10 - G1082A polymorphism analysis was done by Polymerase chain reaction — Restricted fraction length polymorphism ( PCR - RFLP) ,-20ul of the products were insolated in 4% agarose gel electrophoresis, then dyed and observed. Finally, chi square test was used to detect the differ of genotype-frequency between two groups ( P < 0.05).Results1. The distribution frequency of AA, AG, GG genotypes of IL - 10 -G1082A in population of North China were 88. 5% ,10.9% ,0. 6% respectively. There were no differences that distribution frequency of IL - 10 - G1082A AG + GG genotype in population of North China on regions and genders(P >0.05).2. The distribution frequency of IL - 10 - 1082 AG + GG genotype in gastric cancer patients was significantly higher than that in non - cancer control subjects ( P = 0. 006 ) and healthy control subjects (P = 0. 003 ).3. Compared with normal subjects with IL - 10 - 1082 AA genotype and HPIgG antibody negative, the gastric cancesr onset risk of subjects with IL -10- 1082AG + GG genotype and HPIgG antibody negative rised 3. 302 times (P =0.011,95%CI;1.273 -8.566) , the gastric cancesr onset risk of subjects with IL -10 - 1082AA genotype and HPIgG antibody positive rised 4. 315 times ( P = 0.000,95%CI: 1.957 -9.514) , the gastric cancesr onset risk of subjects with IL - 10 - 1082AG + GG genotype and HPIgG antibody positive rised 2. 541 times ( P = 0. 001,95% CI :2.090 - 3.089). Compared with subjects with IL - 10 -1082 AG + GG genotype and HPIgG antibody positive, there was no significant difference in gastric cancesr onset risk of subjects with IL - 10 - 1082AA genotype and HPIgG antibody positive .Conclusions1. The risk of gastric cancer in population with IL - 10 - 1082 AG + GG genetype was high.2. There are no synergism between IL - 10 - G1082A promoter polymorphism and H. pylori infection during the development of gastric cancer.