BACKGROUND: Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations.OBJECTIVE: To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1β −511C→T [rs16944], IL-4 receptor [IL-4R] −3223C→T [rs2057768], IL-8 −251T→A [rs4073], IL-10 −1082A→G [rs1800896] and tumour necrosis factor-alpha −308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population.METHODS: A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the χ2 test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI.RESULTS: A significant association between the IL-4R −3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R −3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R −3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms.CONCLUSION: The results suggest that the IL-4R −3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.