To investigate whether genetic differences in cytokine promoter polymorphisms effect various outcomes after exposure to Epstein-Barr virus (EBV) infection, 30 patients with EBV-positive gastric carcinoma (GC), 120 patients with EBV-negative GC, and 220 control subjects were enrolled. Promoter polymorphisms of tumor necrosis factor (TNF)-alpha at positions -238 and -308 and of interleukin (IL)-10 at position -1082 were determined. The frequency of the high-producer allele (-308A) in the TNF-alpha gene was significantly higher among EBV-positive GC patients compared with control subjects (23.3% vs. 12.0%, P<.05), whereas the frequency of the high-producer allele (-1082G) in the IL-10 gene was significantly higher among EBV-negative GC patients compared with control subjects (6.3% vs. 3.0%, P<.05). These data support the notion that genetic factors may modify the outcomes of infectious diseases through different TNF-alpha- or IL-10-producing capabilities.