Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer |
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| Authors: | Takeichi Yoshida Jun Kato Izumi Inoue Noriko Yoshimura Hisanobu Deguchi Chizu Mukoubayashi Masashi Oka Mika Watanabe Shotaro Enomoto Toru Niwa Takao Maekita Mikitaka Iguchi Hideyuki Tamai Hirotoshi Utsunomiya Nobutake Yamamichi Mitsuhiro Fujishiro Masataka Iwane Tatsuya Takeshita Toshikazu Ushijima Masao Ichinose |
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| Affiliation: | 1. Second Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan;2. Department of Joint Disease Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;3. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;4. Wakayama Wellness Foundation, Wakayama, Japan;5. Department of Public Health, School of Medicine, Wakayama Medical University, Wakayama, Japan;6. Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan |
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| 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. |
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| Keywords: | atrophic gastritis Helicobacter pylori cohort study pepsinogen cancer high‐risk gastric cancer |
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