| Background and AimGastric cancer (GC) is the second leading cause of cancer death in the world and particularly prevalent in certain countries including China. Helicobacter pylori (H. pylori) is a major cause of chronic gastritis and duodenal ulcer, and a definite carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms have not been fully understood, although the interactions between environmental, bacterial and multiple genetic components are likely to be involved. Interleukin-1( IL-1) and Tumor necrosis factor (TNF) are a key cytokines involved in H. pylori-induced gastric inflammation. Present study aimed to determine the di-allelic polymorphisms of IL-1, TNF gene and their association with H. pylori infection and gastroduodenal diseases in Han nationality population of Henan province in China. To evaluate the association between IL-1,TNF loci polymorphisms and increased risk of gastric carcinoma in samples from Han population of HenanProvince.MethodsSubjects were divided into two groups, 83 patients of group 1 with gastric cancer (GC) and 152 patients of group 2 excluded gastroduodenal diseases in the same period were studied. All subjects were recruited by age, sex, family history of gastric cancer, pathological diagnosis. None of these subjects had a history of systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, or inflammatory bowel disease. The diagnosis of gastroduodenal diseases was based on endoscopic and histopathological examinations. Polymorphisms in IL-1B that encodes IL-1βwas analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), IL-1RN that encodes IL-1 receptor antagonist was analyzed by polymerase chain reaction directly; Similarly, Polymorphisms in TNF-a that encodes TNF-αwas analyzed by polymerase chain reaction-restriction fragment length polymorphism. These polymorphic sites include promoter regions of IL-1B at positions-511 (C-T transition), and -31 (C-T transition), and IL-1RN variable tandem repeats, and promoter regions of TNF-a at positions-308(G-A) et al. H. pylori infection status was diagnosed through serum H. Pylori-IgG test by ELISA.Results1. The infection positive rate of H. pylori infection is 55.3% in Han population of Henan province. H. pylori infection was detected in 55.3% of cases (59/83) and 55.3% of controls(84/152) and significant differences were observed between cases and controls (x~2=5.6 P<0.05 ). H. pylori infection was significantly associated with gastric cancer (OR=5.9, 95%CI:3.5-9.9).2. The Allele frequency and Genotype frequencies of IL-1B-31,IL-1B-511 TNF-a-308 were conformed to Hardy-Weinberg Equilibrium. So we can also think the samples mate at random and can represent the population better.3. The genotypes of IL-1B-31 alleles were C/C, C/T and T/T, The allele frequencies in patients were 12.0%, 45.8%, 42.2% and the frequencies in controls were 24.3%. 40.1%, 35.5%, no significant differences were observed between cases and controls in genotype of C/C and C/T(P<0.05); contrast the genotype of C/C, IL-1B-31 T/T carriers were at an increase risk of gastric cancer with an odds ratio of 6.5 (95%CI: 1.2-8.3).4. The genotypes of IL-1B-511 alleles were C/C, C/T and T/T, The frequencies in patients were 18.0%, 41.0%, 41.0% and the frequencies in controls were 23.0 %, 50.0%, 27.0%, no significant differences were observed between cases and controls in genotype of C/C and C/T (P＜0.05); contrast the genotype of C/C, IL-1B-511 T/T carriers were at an increase risk of gastric cancer with an odds ratio of 3.2 (95%CI: 1.1-4.5).5. Five kinds of genotypes of IL-1RN were found as I/I, I/II ,I/III, I/IV, II/II, and the frequencies in patients were 80.7%,14.5%, 0, 3.6% and 1.2% , respectively. However , the frequencies in controls were 78.9%, 13.8%, 1.3% and 3.92%. No significant differences were observed between cases and controls in each genotype.6. The genotypes of TNF-a-308 alleles were G/G, G/A and A/A. The frequencies in patients were 90.4%, 9.6%, 0% and the frequencies in controls were 88.2%, 10.5%, 1.3%; No significant differences were observed between cases and controls in each genotype.7. We found the distribution of IL-1B-31 has no significant differences with the distribution in Japan, but significant differences with the distribution in Korea(P <0.05); similarly, the distribution of IL-1B-511 has no significant differences with the distribution in Xi'an city, Taiwan, and Korea, but significant differences with the distribution in Japan, England et al.(P<0.05); the distribution of IL-1RN has no significant differences with the distribution in Guangdong province, Korea, but significant differences with the distribution in Beijing, Japan, England et al.(P <0.05); the distribution of TNF-a-308 has no significant differences with the distribution in Fujian province, Korea, et al, but significant differences with the distribution in Italy, England et al (P<0.05).8. The genotypes of IL-1B-31T/T,IL-1B-511T/T and H. pylori infection association achieved significance at P=0.05 when we used multivariable logistic regression analysis for risks of gastric cancer (OR=4.89 95%CI:1.51-15.89; OR-7.52 95%C1:2.68-18.71; OR=11.31 95%CI:3.46-28.69 ).Conclusions1. We found the significant differences between H. Pylori infection and gastric cancer, H. Pylori infection may cooperate with IL-IB gene polymorphisms in the development of gastric cancer.2. C/T of IL-1B-31,IL-1B-511 and I/I of IL-IRN and G/G of TNF-a-308 were the main genotypes both in cases and controls in Henan Province. Significant differences were observed between race and countries or areas in the allele frequency of IL-1B,IL-1RN and TNF-a-308.3. In Han population of Henan province, the polymorphism of IL-1B-31T/T and IL-1B-511T/T alleles may be associated with the susceptibility of gastric cancer. However, no evidence was found to support that the polymorphisms of IL-1RN and TNF-a-308 alleles had relationship with gastric cancer.
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