Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer
Open Access
- 5 September 2013
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 134 (6), 1445-1457
- https://doi.org/10.1002/ijc.28470
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.This publication has 44 references indexed in Scilit:
- Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritisAlimentary Pharmacology & Therapeutics, 2010
- Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesionInternational Journal of Cancer, 2009
- Cancer High-Risk Subjects Identified by Serum Pepsinogen Tests: Outcomes after 10-Year Follow-up in Asymptomatic Middle-Aged MalesCancer Epidemiology, Biomarkers & Prevention, 2008
- Pathology and molecular biology of gastric cancerBest Practice & Research Clinical Gastroenterology, 2006
- Gastric cancer screening of a high‐risk population in Japan using serum pepsinogen and barium digital radiographyCancer Science, 2005
- Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbilsBiochemical and Biophysical Research Communications, 2005
- Synergistic Promoting Effects of Helicobacter pylori Infection and High‐salt Diet on Gastric Carcinogenesis in Mongolian GerbilsJapanese Journal of Cancer Research, 2002
- Gastric cancer and Helicobacter pyloriAlimentary Pharmacology & Therapeutics, 2002
- Helicobacter pyloriInfection and the Development of Gastric CancerThe New England Journal of Medicine, 2001
- Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancerInternational Journal of Cancer, 1999