Gastric carcinogenesis is a multistep process progressing from chronic gastritis, through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. We have previously demonstrated that minority patients at New York City hospitals are infected with a relatively virulent strain of H. pylori (Hp) and that Hp infection is associated with an increased incidence of precancerous changes in the gastric mucosa. Nevertheless, precancerous changes are not observed in every Hp-infected individual, suggesting that environmental and genetic factors may also play a role in the formation and appearance of precancerous lesions. In the present study, the association between polymorphisms in the promoter regions of human myeloperoxidase (MPO-463G¨A) and catalase (CAT-262C¨T) genes and the appearance of precancerous changes in the gastric mucosa of our patient population were examined. Patients enrolled in this study were undergoing endoscopy for gastrointestinal complaints. Samples were collected from 126 patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital in Queens. One antral biopsy was taken for genotyping, while additional biopsies were taken from the antrum and fundic region for histological analysis and were scored with respect to acute and chronic inflammation, GA, IM and Hp infestation according to the Sydney classification. MPO and CAT genotypes were determined by PCR and RFLP. CAT genotypes did not influence the incidence or severity of precancerous lesions in the fundic or antral regions of the stomach, whereas the MPO-463A allele was associated with an increase in intensity of gastric atrophy in the fundic mucosa. In Hp-infected individuals, the MPO-463G/G genotype was associated with an increase in the incidence of IM in the antrum, whereas the A allele was associated with an increase in IM in the fundic region. These paradoxical findings suggest that different MPO genotypes are associated with the appearance of IM in distinct anatomical regions of the stomach. However, since the majority of gastric cancer (GC) cases in our patient population occurred in the antrum, the MPO-463G/G genotype, which is associated with increased MPO expression and antral IM, may be considered a risk factor for GC.