BACKGROUND: Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population.OBJECTIVE: To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pyloriand cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people.METHODS: The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors forH pyloriinfection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer.RESULTS: A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoingH pyloriinfection as measured by anti-H pyloriantibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pyloriantibodies compared with their matched controls (P=0.01). In a multivariate model, non-cardia gastric cancer (n=94) was associated with anti-H pyloriantibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found.CONCLUSION: Alaska Native people with gastric cancer had increased odds of previousH pyloriinfection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.