High-Negative Anti- Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan

Cancer Epidemiol Biomarkers Prev. 2020 Feb;29(2):420-426. doi: 10.1158/1055-9965.EPI-19-0993. Epub 2019 Dec 11.


Background: Serologic testing of anti-Helicobacter pylori antibody, together with testing of pepsinogen I and II, is now widely used to stratify groups at high risk of gastric cancer in Japan. Those with a negative anti-H. pylori IgG titer, especially "high-negative" (3-<10 U/mL), are speculated to have higher risk of gastric cancer. We aimed to evaluate the association between a high-negative anti-H. pylori IgG titer and the long-term risk of gastric cancer in the Japan Public Health Center-based Prospective Study (JPHC Study) Cohort II.

Methods: The study population consisted of 19,106 Japanese men and women who were followed from 1993 to 2013. A Cox proportional hazards model was used to assess the risk of gastric cancer for plasma anti-H. pylori IgG titers, together with the severity of atrophic gastritis by pepsinogen I and II levels. A total of 595 cases of gastric cancer occurred during an average of 18 years of follow-up.

Results: Compared with those with a low-negative anti-H. pylori IgG titer (≤3 U/mL), subjects with a high-negative titer (3-<10 U/mL) showed a significantly elevated risk of gastric cancer [HR = 2.81; 95% confidence interval (CI) = 1.62-4.89]. Among those with a high-negative titer, risk increase was observed under moderate or severe atrophic gastritis (HR = 18.73; 95% CI = 8.83-39.70).

Conclusions: Our results suggest that those with a high-negative anti-H. pylori IgG titer and moderate and severe atrophic gastritis are at increased long-term risk of gastric cancer.

Impact: Development of moderate or severe atrophic gastritis in subjects with high-negative anti-H. pylori IgG titer is suggested to increase risk of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Bacterial / blood*
  • Antibodies, Bacterial / immunology
  • Female
  • Follow-Up Studies
  • Gastritis, Atrophic / blood
  • Gastritis, Atrophic / diagnosis*
  • Gastritis, Atrophic / microbiology
  • Gastritis, Atrophic / pathology
  • Helicobacter Infections / blood
  • Helicobacter Infections / diagnosis*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / immunology*
  • Helicobacter pylori / isolation & purification
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Pepsinogen A / blood
  • Pepsinogen C / blood
  • Prospective Studies
  • Risk Assessment
  • Serologic Tests
  • Severity of Illness Index
  • Stomach Neoplasms / epidemiology*


  • Antibodies, Bacterial
  • Immunoglobulin G
  • Pepsinogen C
  • Pepsinogen A