title: Receiver operating characteristic analysis of prediction for gastric cancer development using serum pepsinogen and Helicobacter pylori antibody tests.
abstract: Chronic Helicobacter pylori infection plays a central role in the development of gastric cancer as shown by biological and epidemiological studies. The H. pylori antibody and serum pepsinogen (PG) tests have been anticipated to predict gastric cancer development.
  
  
  
  We determined the predictive sensitivity and specificity of gastric cancer development using these tests. Receiver operating characteristic analysis was performed, and areas under the curve were estimated. The predictive sensitivity and specificity of gastric cancer development were compared among single tests and combined methods using serum pepsinogen and H. pylori antibody tests.
  
  
  
  From a large-scale population-based cohort of over 100,000 subjects followed between 1990 and 2004, 497 gastric cancer subjects and 497 matched healthy controls were chosen. The predictive sensitivity and specificity were low in all single tests and combination methods. The highest predictive sensitivity and specificity were obtained for the serum PG I/II ratio. The optimal PG I/II cut-off values were 2.5 and 3.0. At a PG I/II cut-off value of 3.0, the sensitivity was 86.9% and the specificity was 39.8%. Even if three biomarkers were combined, the sensitivity was 97.2% and the specificity was 21.1% when the cut-off values were 3.0 for PG I/II, 70 ng/mL for PG I, and 10.0 U/mL for H. pylori antibody.
  
  
  
  The predictive accuracy of gastric cancer development was low with the serum pepsinogen and H. pylori antibody tests even if these tests were combined. To adopt these biomarkers for gastric cancer screening, a high specificity is required. When these tests are adopted for gastric cancer screening, they should be carefully interpreted with a clear understanding of their limitations.
authors.affiliation: Division of Cancer Screening Assessment and Management, Center for Social Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan. chamashi@ncc.go.jp.
authors.forename: Chisato
authors.identifier: 0000-0003-2585-8479
authors.initials: C
authors.lastname: Hamashima
authors.affiliation: Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sasazuki
authors.affiliation: Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.|Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D016481:Helicobacter Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood*; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology / Q000382:microbiology*
chemical_list: D000907:Antibodies, Bacterial; D014408:Biomarkers, Tumor; D020116:Pepsinogen A
keywords: Cancer screening; Gastric cancer; Helicobacter pylori antibody; Receiver operating characteristic analysis; Serum pepsinogen