AIM: To study whether examination of CagA antibodies could increase the odds ratio for gastric cancer in a casecontrol study, and how often other serum markers of gastric cancer risk could be found in Helicobacter pylorinegative patients.METHODS: H pylori CagA and parietal cell antibodies(PCAs), and serum pepsinogen Ⅰ (SPGI) levels were compared between patients with gastric cancer and controls who received endoscopic examination due to reasons other than gastrointestinal malignancy.RESULTS: The odds ratio (OR) for gastric cancer was2.9 (95% CI 1.4-5.8) in H pylori+ patients, and 2.4 (95%CI 1.2-4.9) in CagA+ patients. When results of H pylori and CagA antibodies were combined, OR increased to5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were excluded, the OR increased to 6.8 (95% CI3.1-14.8). Among patients with a low SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant only in the older age group. The number of patients with low SPGI was significantly higher in H pylori-/CagA+ patients as compared to other cancer patients.CONCLUSION: Examination of both H pylori and CagA antibodies increases the OR for gastric cancer in our casecontrol study. CagA antibodies are important in detecting previous H pylori infection in advanced atrophic gastritis or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be helpful in screening elderly gastric cancer patients.