Cancer risk to the gastric corpus in Japanese, its correlation with Interleukin-1β 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-1β 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-1β 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-1β gene polymorphisms, genotype IL-1β+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-1β+3953 T/T in either group. Thus, the effect of IL-1β+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-1β+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.