Polymorphism of hOGG1 may be capable of serving as a genetic marker for individual susceptibility to various cancers because of its role in the repair of oxyradical DNA damage. We examined the distribution of the hOGG1 Ser326Cys polymorphism and its presumed correlation with gastric cancer risk in two case-control studies of different ethnic groups in São Paulo, Brazil. Potentially eligible Japanese (JB) and non-Japanese Brazilian (NJB) case subjects were defined as patients with newly diagnosed malignant neoplasms of the stomach in 13 hospitals in São Paulo. Ninety-six JBs and 236 NJBs were adopted as subjects. Two controls were matched for each JB case, and one control for each NJB case. The subjects were interviewed using a questionnaire and their blood samples were collected. A significant difference in the distribution of this polymorphism between the two ethnic groups was observed (chi(2)=58.3, P<0.01). The mutant type (Ser/Cys or Cys/Cys) was predominant (approximately 65%) in the JBs, but was only present in approximately 40% of the NJBs. Logistic regression analysis showed no significant increased risk for either the Ser/Cys or Cys/Cys type in either group. The odds ratios of the Cys allele for gastric cancer were 1.01 (95% confidence interval (CI): 0.52-1.93) in the JBs and 0.85 (95% CI: 0.57-1.26) in the NJBs. In the NJBs, a significant increased risk of smoking was shown only in the Ser/Ser type, and no increased risk was shown in the genotypes with the Cys allele. However, no statistically significant interactions were observed with smoking or other possible confounding factors. No statistically significant difference in the distribution of the polymorphism was observed between the intestinal type and diffuse type of gastric cancer in either the JBs or the NJBs. The ethnic difference in hOGG1 Ser326Cys polymorphism was much greater than the case-control difference, and this polymorphism is unlikely to be associated with gastric cancer.