Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori) infection or smoking may be a cause of gastric cancer development. 8-Hydroxydeoxyguanine (8-OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGGl) is responsible for repairing 8-OHdG lesions. Among several hOGGl gene polymorphisms, the SerCys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGGl polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case-control study with 142 histologically-confirmed gastric cancer cases and 271 age, sex-matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGGl Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction =0.03). No significant interaction was found between hOGGl genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGGl Cys allele might have a higher susceptibility to gastric cancer.