Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle‐aged men who were H. pylori antibody‐positive and pepsinogen (PG) test‐negative. Subjects were stratified according to the activity of H. pylori‐associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person‐years), with 85.7% developing in the group showing a PGI/II ratio ≤3.0, reflecting active inflammation‐based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person‐years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low‐titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high‐risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori‐infected nonatrophic stomach.

[1]  T. Hibi,et al.  H. pylori-Eradication Therapy Increases RUNX3 Expression in the Glandular Epithelial Cells in Enlarged-Fold Gastritis , 2010, Journal of clinical biochemistry and nutrition.

[2]  Takeshi Toyoda,et al.  Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. , 2010, Cancer research.

[3]  N. Yoshimura,et al.  Eradication of Helicobacter pylori prevents cancer development in subjects with mild gastric atrophy identified by serum pepsinogen levels , 2009, International journal of cancer.

[4]  Y. Yamaoka,et al.  Helicobacter pylori typing as a tool for tracking human migration. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[5]  S. Devesa,et al.  Stomach Carcinoma Incidence Patterns in the United States by Histologic Type and Anatomic Site , 2009, Cancer Epidemiology Biomarkers & Prevention.

[6]  N. Yamamichi,et al.  Risk of gastric cancer in asymptomatic, middle‐aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels , 2008, International journal of cancer.

[7]  N. Yoshimura,et al.  Cancer High-Risk Subjects Identified by Serum Pepsinogen Tests: Outcomes after 10-Year Follow-up in Asymptomatic Middle-Aged Males , 2008, Cancer Epidemiology Biomarkers & Prevention.

[8]  N. Hayashi,et al.  E‐cadherin Gene Promoter Hypermethylation in H. pylori‐Induced Enlarged Fold Gastritis , 2007, Helicobacter.

[9]  P. Correa,et al.  Carcinogenesis of Helicobacter pylori. , 2007, Gastroenterology.

[10]  Y. Hirooka,et al.  Rugal hyperplastic gastritis increases the risk of gastric carcinoma, especially diffuse and p53-independent subtypes , 2007, European journal of gastroenterology & hepatology.

[11]  W. Leung,et al.  Effects of Helicobacter pylori Eradication on Methylation Status of E-Cadherin Gene in Noncancerous Stomach , 2006, Clinical Cancer Research.

[12]  M. Toyota,et al.  Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein–Barr virus , 2006, Cancer.

[13]  A. Kaneda,et al.  High Levels of Aberrant DNA Methylation in Helicobacter pylori–Infected Gastric Mucosae and its Possible Association with Gastric Cancer Risk , 2006, Clinical Cancer Research.

[14]  B. C. Wong,et al.  Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation , 2006, Gut.

[15]  G. Tamura.  Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. , 2006, World journal of gastroenterology.

[16]  N. Yoshimura,et al.  Gastric cancer screening of a high‐risk population in Japan using serum pepsinogen and barium digital radiography , 2005, Cancer science.

[17]  Y. Yamaji,et al.  Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study , 2005, Gut.

[18]  P. Malfertheiner,et al.  Helicobacter pylori and molecular events in precancerous gastric lesions , 2004, Alimentary pharmacology & therapeutics.

[19]  N. Hamajima,et al.  The association between tumour necrosis factor-α gene polymorphism and the susceptibility to rugal hyperplastic gastritis and gastric carcinoma , 2004, European journal of gastroenterology & hepatology.

[20]  N. Yoshimura,et al.  Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer , 2004, International journal of cancer.

[21]  Mitsuru Sasako,et al.  Focus on gastric cancer. , 2004, Cancer cell.

[22]  S. Leung,et al.  Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. , 2004, JAMA.

[23]  T. Yoshimura,et al.  Time trend analysis of gastric cancer incidence in Japan by histological types, 1975-1989 , 2001, British Journal of Cancer.

[24]  M. Inoue,et al.  Severity of chronic atrophic gastritis and subsequent gastric cancer occurrence: a 10-year prospective cohort study in Japan. , 2000, Cancer letters.

[25]  E. Kuipers,et al.  IgG antibody titer against Helicobacter pylori correlates with presence of cytotoxin associated gene A-positive H. pylori strains. , 2000, FEMS immunology and medical microbiology.

[26]  S. D. Lee,et al.  Serodiagnosis of Helicobacter pylori infection: comparison and correlation between enzyme-linked immunosorbent assay and rapid serological test results , 1997, Journal of clinical microbiology.

[27]  Y. Matsuzawa,et al.  Increased production of interleukin 1 beta and hepatocyte growth factor may contribute to foveolar hyperplasia in enlarged fold gastritis. , 1996, Gut.

[28]  M. Rugge,et al.  Helicobacter pylori serology in patients with chronic gastritis. , 1996, The American journal of gastroenterology.

[29]  M. Stolte,et al.  Helicobacter pylori eradication in the treatment and differential diagnosis of giant folds in the corpus and fundus of the stomach. , 1995, Zeitschrift fur Gastroenterologie.

[30]  M. Stolte,et al.  Giant fold gastritis--a special form of Helicobacter pylori associated gastritis. , 1993, Zeitschrift fur Gastroenterologie.

[31]  A. Oshima,et al.  Fundal atrophic gastritis as a risk factor for gastric cancer , 1993, International journal of cancer.

[32]  P. Correa,et al.  Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. , 1992, Cancer research.

[33]  P. Sipponen,et al.  Helicobacter pylori infection and chronic gastritis in gastric cancer. , 1992, Journal of clinical pathology.

[34]  W. Karnes,et al.  Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. , 1991, Gastroenterology.

[35]  G. Tytgat.  The Sydney System: Endoscopic division. Endoscopic appearances in gastritis/duodenitis , 1991, Journal of gastroenterology and hepatology.

[36]  S. Czinn,et al.  Enlarged gastric folds in association with Campylobacter pylori gastritis. , 1989, Radiology.

[37]  E. Masci,et al.  Gastric cancer in chronic atrophic gastritis. Associated gastric ulcer adds no further risk. , 1987, Journal of clinical gastroenterology.

[38]  J. Haapakoski,et al.  Gastric cancer risk in chronic atrophic gastritis: Statistical calculations of cross‐sectional data , 1985, International journal of cancer.

[39]  K. Miki,et al.  Radioimmunoassay of serum group I and group II pepsinogens in normal controls and patients with various disorders. , 1982, Clinica chimica acta; international journal of clinical chemistry.

[40]  E. Balthazar,et al.  Hyperrugosity in gastric carcinoma: radiographic, endoscopic, and pathologic features. , 1981, AJR. American journal of roentgenology.

[41]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.

[42]  西林 宏之.  Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma , 2008 .

[43]  Hanna Vauhkonen,et al.  Pathology and molecular biology of gastric cancer. , 2006, Best practice & research. Clinical gastroenterology.

[44]  R. P. Blankfield,et al.  Helicobacter pylori infection and the development of gastric cancer. , 2001, The New England journal of medicine.

[45]  Songjun,et al.  Morphological and Functional Restoration of Parietal Cells in Helicobacter pylori Associated Enlarged Fold Gastritis after Eradication , 2000 .

[46]  M. Rugge,et al.  Prevalence of Helicobacter pylori infection in patients with precancerous changes and gastric cancer. , 1993, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[47]  M. Wiljasalo,et al.  Studies of patients with atrophic gastritis: a 10-15-year follow-up. , 1966, Scandinavian journal of gastroenterology.