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Polymorphisms ofinterleukin-1 (IL-1)genes have been reported to modify the risk of gastric carcinoma (GC) in Caucasians. The significance ofIL-1βgene polymorphisms was evaluated in Japanese GC patients with or without infection ofHelicobacter pyloriand Epstein Barr virus (EBV) with special reference to the topographic features of GC.IL-1βgene polymorphisms at positions -511 and +3953 were evaluated by PCR-RFLP and a penta-allelic polymorphism ofIL-1RAby PCR in healthy controls (n= 103) and GC (n=140; corpus 95, antrum 45). EBV-infection was determined in the neoplastic tissues byEBER1 in situhybridization, andH. pyloriinfection in nonneoplastic gastric mucosa by PCR targeting of theH. pylori urease Agene. GC consisted of EBV-associated (n= 24) and EBV-negative (n= 116) patients, whereasH. pyloriinfection was positive in 130 cases. AmongIL-1βgene polymorphisms, genotypeIL-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 genotypeIL-1β+3953 T/T in either group. Thus, the effect ofIL-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 ofIL-1gene 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 betweenH. pyloriinfection andIL-1gene polymorphism in GC. The cancer risk of the gastric corpus in Japanese is influenced byIL-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. © 2005 Wiley-Liss, Inc.