title: Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study.
abstract: BACKGROUND
  Although accumulating evidence suggests that Helicobacter pylori plays a role in gastric carcinogenesis, the magnitude of the risk remains uncertain.
  
  
  OBJECTIVE
  We aimed to estimate the magnitude of the risk of gastric cancer associated with H. pylori infection by a large case-control study nested within a prospective cohort. Possible effect modification by CagA status, and serum pepsinogen status, as a marker of atrophic gastritis, was also considered to see its effect on developing gastric cancer.
  
  
  METHODS
  Subjects (n = 123,576) were followed up from 1990 to 2004; 511 gastric cancer cases matched to 511 controls were used in the analysis. Plasma immunoglobulin G antibody to H. pylori, CagA, and pepsinogen I and II were measured.
  
  
  RESULTS
  The adjusted odds ratio (95% confidence interval) of gastric cancer associated with H. pylori infection was 5.1 (3.2-8.0). Assuming all CagA-positive subjects are true H. pylori positives doubled this risk. Atrophic gastritis was also associated with an elevated risk of gastric cancer and the risk increased further with pepsinogen levels.
  
  
  CONCLUSIONS
  Subjects with pepsinogen levels indicative of severe atrophic gastritis may need careful examination regularly regardless of H. pylori infection. Those who have other pepsinogen levels but who are H. pylori seropositive are likely to benefit from H. pylori eradication therapy. Considering both the cost and the potential for misclassification that may occur using multiple serologic tests, caution is needed in interpreting or extrapolating these findings into a screening strategy.
authors.affiliation: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Chuo-ku, Tokyo, Japan. ssasazuk@gan2.res.ncc.go.jp
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sasazuki
authors.forename: Manami
authors.initials: M
authors.lastname: Inoue
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Otani
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hanaoka
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000453:epidemiology / Q000821:virology; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005757:Gastritis, Atrophic / Q000097:blood / Q000453:epidemiology / Q000821:virology; D016481:Helicobacter Infections / Q000097:blood / Q000150:complications* / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020116:Pepsinogen A / Q000097:blood*; D020115:Pepsinogen C / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013274:Stomach Neoplasms / Q000097:blood / Q000453:epidemiology / Q000821:virology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C080866:cagA protein, Helicobacter pylori; D020115:Pepsinogen C; D020116:Pepsinogen A