Family History of Gastric Cancer and Helicobacter pylori Treatment

N Engl J Med. 2020 Jan 30;382(5):427-436. doi: 10.1056/NEJMoa1909666.

Abstract

Background: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown.

Methods: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period.

Results: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).

Conclusions: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / epidemiology
  • Adenoma / etiology
  • Adenoma / prevention & control
  • Adult
  • Aged
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Lansoprazole / therapeutic use
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Republic of Korea
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / prevention & control*

Substances

  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Lansoprazole
  • Amoxicillin
  • Clarithromycin

Associated data

  • ClinicalTrials.gov/NCT01678027