Treatment of Helicobacter Pylori Infection May Reduce the Risk of Gastric Cancer in First-Degree Relatives of Patients with Gastric Cancer

Findings from a prospective, double-blind, placebo-controlled trial conducted in South Korea
13 Feb 2020

Findings from a study performed in South Korea among persons with Helicobacter pylori infection who had a family history of gastric cancer in first-degree relatives, show that Helicobacter pylori eradication treatment reduced the risk of gastric cancer. The results from this randomised trial are published on 30 January 2020 in The New England Journal of Medicine.

Helicobacter pylori infection is a common bacterial infection that affects more than half of the world population. Case–control studies performed in the US showed an association between Helicobacter pylori infection and gastric cancer and a long-term observational study from Japan showed that gastric cancer developed only in patients with Helicobacter pylori infection who had various gastric diseases. Recent randomised study that involved patients with early gastric cancer in South Korea showed that treatment of Helicobacter pylori infection reduced the risk of metachronous gastric cancer by 50%.

Treatment of Helicobacter pylori infection in the general population to prevent gastric cancer is supported by moderate evidence based on findings from a meta-analysis of six randomised trials. The International Agency for Research on Cancer suggested that population-based screening and treatment for Helicobacter pylori infection should be tailored to local conditions. Further studies are needed to investigate the feasibility, efficacy, and adverse consequences of this strategy.

A family history of gastric cancer in a first-degree relative is associated with double to triple the risk of gastric cancer. Patients with gastric cancer and their relatives share risk factors, including exposure to Helicobacter pylori and genetic features that may affect immune responses to Helicobacter pylori infection. Family members of patients with gastric cancer have higher rates of Helicobacter pylori infection than persons in the general population. The precancerous histologic changes in the gastric mucosa are more severe in these persons.

The authors wrote in the study background that it is unclear whether treatment of Helicobacter pylori infection can reduce the risk of gastric cancer because of a lack of evidence. Therefore, they performed a single-centre, double-blind, placebo-controlled trial, and screened 3100 first-degree relatives of patients with gastric cancer. They randomly assigned 1838 participants with Helicobacter pylori infection to receive either eradication therapy consisting of 30 mg lansoprazole, 1000 mg amoxicillin, and 500 mg clarithromycin, each taken twice daily for 7 days or placebo.

The primary outcome of the study was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to Helicobacter pylori eradication status, assessed during the follow-up period.

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, 10 participants developed gastric cancer (1.2%) in the treatment group and 23 (2.7%) in the placebo group (hazard ratio [HR], 0.45; 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 Helicobacter pylori infection.

Gastric cancer developed in 5 of 608 (0.8%) participants in whom Helicobacter pylori infection was eradicated and in 28 of 979 (2.9%) participants who had persistent infection (HR 0.27). 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).

The study team concluded that in this prospective, randomised trial involving first-degree relatives of patients with gastric cancer, the risk of gastric cancer was 55% lower among those who received Helicobacter pylori eradication treatment than among those who received placebo, during a median follow-up of 9.2 years. The risk of gastric cancer was 73% lower among persons in whom Helicobacter pylori eradication was achieved than among those in whom infection was persistent.

The authors wrote that the main advantage of their trial is that the incidence of gastric cancer was evaluated as the primary outcome in a large-scale, long-term trial. However, the study has several limitations, for example recruitment in a single center. The authors underlined the fact that the Korean population is of the same ethnic group and that there is little geographic variation in the incidence of gastric cancer, so it may support the generalisability of the findings to the rest of South Korea. They also emphasised that family history is a consistent risk factor worldwide, so their results may be globally applicable. 

Regarding an ethical issue about conducting a trial with the use of placebo, the authors wrote that the health insurance system in South Korea does not cover Helicobacter pylori therapy in trial population. But the investigators provided eradication therapy to all participants who still had Helicobacter pylori infection at the end of the trial. 

The study team did not evaluate the genetic susceptibility of the participants to gastric cancer or the bacterial virulence factors of Helicobacter pylori, which may be risk factors for gastric cancer.

 

Reference

Choi IJ, Kim CG, Lee JY, et al. Family History of Gastric Cancer and Helicobacter pylori Treatment. NEJM 2020; 382(5):427-436. DOI: 10.1056/NEJMoa1909666.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings