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Cancer High-Risk Subjects Identified by Serum Pepsinogen Tests: Outcomes after 10-Year Follow-up in Asymptomatic Middle-Aged Males

Departments of ¹ Gastroenterology and ² Public Health, School of Medicine, Wakayama Medical University; ³ Wakayama Wellness Foundation, Wakayama City, Wakayama, Japan; and Departments of ⁴ Joint Disease Research and ⁵ Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Requests for reprints: Masao Ichinose, Department of Gastroenterology, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-0012, Japan. Phone: 81-734-47-1335; Fax: 81-734-45-3616. E-mail: ichinose{at}wakayama-med.ac.jp

Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study.

Methods: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on "atrophy-positive" and "atrophy-negative" criteria used for cancer screening was investigated.

Results: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, 70 ng/mL; pepsinogen I/II ratio, 3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive value. Cancer incidence rate was 276 per 100,000 person-years for the atrophy-positive group and 70 per 100,000 person-years for the atrophy-negative group. Incidence rate was higher in groups fulfilling stricter positive criteria detecting more extensive atrophy, reaching 424 per 100,000 person-years. In addition, 9.2% of atrophy-negative subjects with pepsinogen I of >70 ng/mL and pepsinogen I/II ratio of 3.0 (reflecting putative inflammation-based high pepsinogen II level) are at high risk for cancer, particularly diffuse-type cancer, with a cancer incidence rate comparable with atrophy-positive subjects (216 per 100,000 person-years).

Conclusion: Atrophy-positive subjects by pepsinogen filter test, particularly those fulfilling stricter criteria, and atrophy-negative subjects with low pepsinogen I/II ratio reflecting putative extensive active inflammation constitute populations at high risk for gastric cancer, requiring thorough endoscopic examination. (Cancer Epidemiol Biomarkers Prev 2008;17(4):838–45)