title: Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer.
abstract: Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan.
authors.forename: Takeichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Izumi
authors.initials: I
authors.lastname: Inoue
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Deguchi
authors.forename: Chizu
authors.initials: C
authors.lastname: Mukoubayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Oka
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shotaro
authors.initials: S
authors.lastname: Enomoto
authors.forename: Toru
authors.initials: T
authors.lastname: Niwa
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Mikitaka
authors.initials: M
authors.lastname: Iguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamai
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Nobutake
authors.initials: N
authors.lastname: Yamamichi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Masataka
authors.initials: M
authors.lastname: Iwane
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takeshita
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008679:Metaplasia / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood*; D020115:Pepsinogen C / Q000097:blood*; D011379:Prognosis; D011863:Radioimmunoassay; D012307:Risk Factors; D013270:Stomach / Q000473:pathology / Q000821:virology; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology
chemical_list: D000907:Antibodies, Bacterial; D014408:Biomarkers, Tumor; D020115:Pepsinogen C; D020116:Pepsinogen A
keywords: Helicobacter pylori; atrophic gastritis; cancer high-risk; cohort study; gastric cancer; pepsinogen