title: Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer.
abstract: We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.
authors.affiliation: Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohata
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kitauchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Kouichi
authors.initials: K
authors.lastname: Mugitani
authors.forename: Masataka
authors.initials: M
authors.lastname: Iwane
authors.forename: Hideya
authors.initials: H
authors.lastname: Nakamura
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Yanaoka
authors.forename: Kenji
authors.initials: K
authors.lastname: Arii
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamai
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takeshita
authors.forename: Osamu
authors.initials: O
authors.lastname: Mohara
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000328:Adult; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000382:microbiology*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D012307:Risk Factors; D013270:Stomach / Q000382:microbiology; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000382:microbiology; D013997:Time Factors
chemical_list: D020116:Pepsinogen A