The association of cytokine genotypes with gastric carcinoma (GC) may be influenced by environmental factors and varies among different populations. Few studies have addressed the impact of different cytokine genotypes on the development and progression of GC. We analyzed 11 functional polymorphisms in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-4 and IL-10 genes in 220 Taiwanese Chinese with GC and in 230 healthy controls. The risk of genotypes was adjusted with confounding environmental risks. Our results revealed that the frequency of Helicobacter pylori infection [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.19-2.56], cigarette smoking (OR 2.02, 95% CI 1.38-2.95) and high IL-10 producer genotype (OR 2.67, 95% CI 1.29-5.50) was significantly increased in the entire GC patients. Among different subtypes of GC, a higher risk of developing diffuse type (OR 1.64, 95% CI 1.01-2.67) or cardia cancer (OR 2.44, 95% CI 1.13-2.67) was observed for the CT/CC genotype of IL-4 at the position -590, whereas the high IL-10 producer genotype was significantly linked with the risk of cardia cancer (OR 3.21, 95% CI 1.06-9.73) or advanced stage (OR 2.29, 95% CI 1.12-4.64). No association was noted between GC and controls in the distribution of IL-1 and TNF-alpha genotypes. Logistic regression analyses revealed that H. pylori infection (OR 1.7, 95% CI 1.14-2.52), cigarette smoking (OR 1.87, 95% CI 1.27--2.96) and IL-10 genotype (OR 2.54, 95% CI 1.24-5.61) are independent risks for GC. Independent effects of IL-10 genotype, H. pylori infection and cigarette smoking indicate that carcinogenesis of GC is influenced by a variety of host and environmental factors.
Copyright 2003 Wiley-Liss, Inc.