Microsatellite polymorphism in the promoter region of the heme oxygenase-1 (HO-1) gene was analyzed jointly with that of the inducible nitric oxide synthase (iNOS) gene among Japanese subjects (control and gastric cancer patients). A higher promoter activity genotype of the HO-1 gene was associated with increased risk for gastric cancer in women. Gastric cancer risk was notably increased in subjects carrying a higher promoter activity genotype for both HO-1 and iNOS compared to those with a lower promoter activity genotype for both genes. Our data suggest that genetic polymorphisms of HO-1 and iNOS modulate individual susceptibility to gastric cancer risk.