From epidemiological evidence a high salt diet is a risk factor for gastric cancer, independent of Helicobacterpylori infection, and animal studies have shown that salt promotes carcinogenesis. The G-protein β 3(GNB3)C825T polymorphism has been linked with hypertension, salt sensitivity and multiple diseases. Our aim in thisstudy was to clarify any association of the GNB3 C825T polymorphism with gastric cancer risk in Japanese. Weexamined 161 patients with gastric cancer and 183 control subjects. All underwent stomach biopsy by endoscopicprocedures, and extracted DNA was genotyped using a primer pair including the GNB3 C825T polymorphismarea by PCR-based restriction fragment length polymorphism (PCR-RFLP). Logistic-regression analysis wasperformed to assess the impact of the genetic polymorphism. Overall comparison of genotype frequency showedthe CT genotype in control patients to be relatively infrequent, but no statistically significant differences werefound. However, on comparison of subtypes of gastric cancer (intestinal and diffuse), a significantly increasedrisk of diffuse type of gastric cancer was foudn for the TT genotype (odds ratio compared to CC, 3.1, 95%CI1.1-8.6, p=0.03). In conclusion, the TT genotype of GNB3 was associated with diffuse type of gastric cancer. Themechanism of the GNB3 polymorphism interaction with gastric cancer development needs to be clarified byfuture study.