Cancer risk to the gastric corpus in Japanese, its correlation with interleukin-1beta gene polymorphism (+3953*T) and Epstein-Barr virus infection

Polymorphisms of interleukin-1 (IL-1) genes have been reported to modify the risk of gastric carcinoma (GC) in Caucasians. The significance of IL-1beta gene polymorphisms was evaluated in Japanese GC patients with or without infection of Helicobacter pylori and Epstein Barr virus (EBV) with special reference to the topographic features of GC. IL-1beta gene polymorphisms at positions -511 and +3953 were evaluated by PCR-RFLP and a penta-allelic polymorphism of IL-1RA by PCR in healthy controls (n = 103) and GC (n =140; corpus 95, antrum 45). EBV-infection was determined in the neoplastic tissues by EBER1 in situ hybridization, and H. pylori infection in nonneoplastic gastric mucosa by PCR targeting of the H. pylori urease A gene. GC consisted of EBV-associated (n = 24) and EBV-negative (n = 116) patients, whereas H. pylori infection was positive in 130 cases. Among IL-1beta gene polymorphisms, genotype IL-1beta+3953 C/T was more frequent in the EBV-negative (21%) and corpus GC (23%) patients, compared to the controls (10%), respectively, although there was no genotype IL-1beta+3953 T/T in either group. Thus, the effect of IL-1beta+3953 T was statistically significant in logistic regression models adjusted for age in EBV negativity (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.02-5.05) and in the corpus GC (2.70, 1.19-6.12) with highest OR 3.55 (1.54-8.23) in EBV-negative corpus GC. There was no significant influence of IL-1 gene polymorphism in EBV-associated GC, but it occurred predominantly in the corpus (24/24) compared to EBV-negative GC (71/116) (p = 0.00002). There was no correlation between H. pylori infection and IL-1 gene polymorphism in GC. The cancer risk of the gastric corpus in Japanese is influenced by IL-1beta+3953 polymorphisms. On the other hand, the risk of EBV-associated GC, which occurs predominantly in the corpus, is not influenced by this pro-inflammatory polymorphism.     

Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor

Background It is becoming clear that various cytokines are associated with the spread of cancer cells. The purpose of this study was to compare interleukin (IL)-6 levels in patients with gastric cancer to elucidate the role of IL-6 in predicting the spread of tumors.Methods In 60 patients, we assessed the correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic metastasis, and related factors (hepatocyte growth factor [HGF], IL-1, tumor necrosis factor [TNF]-, and transforming growth factor [TGF]-1). We also investigated the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, as well as the association between IL-6 elevation and outcome. Finally, we examined the expression of IL-6 in tumor tissue.Results Significant relationships were seen between serum IL-6 and stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P < 0.05). With regard to the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6 was set at 1.97pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7% and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year cumulative survival rates for patients with an IL-6 value of more than 1.97pg/ml (69.0% and 43.4%, respectively) were significantly lower than those for patients with an IL-6 value of 1.97pg/ml or less (94.4% and 87.2%, respectively; P < 0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells.Conclusion We suspect that IL-6 is involved in cancer invasion and lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be used as a prognostic factor for survival.