Family History of Gastric Cancer and Helicobacter pylori Treatment

Gastric cancer is the fifth leading cause of cancer worldwide, accounting for approximately 8% of cancer cases and 10% of deaths, with the highest burden of disease in developing countries. Specific identifiable risk factors for gastric cancer make it an ideal target for studying cancer prevention. In 1994, the International Agency on the Research of Cancer, a division of the World Health Organization, classified Helicobacter pylori as a class I carcinogen based on its association with gastric cancer. Through several possible mechanisms, family history of gastric cancer is also a strong risk factor.

Although some guidelines support treatment of H. pylori infection in family members of patients with gastric cancer, the 2017 American College of Gastroenterology guidelines state that there is “insufficient evidence to support routine testing and treating of H. pylori in asymptomatic individuals with a family history of gastric cancer.”

In a randomized, placebo-controlled trial recently published in NEJM,  clarithromycin-based treatment of patients with H. pylori infection and a first-degree relative with gastric cancer reduced the incidence of gastric cancer (hazard ratio, 0.45). The incidence of gastric cancer was even lower among those with confirmed H. pylori eradication.

This important proof of concept trial supports the role of H. pylori treatment in carcinogenesis. However, we must be cautious about the generalizability of the results. The trial was conducted in South Korea, which has among the highest prevalence of gastric cancer in the world, and in patients with high baseline risk for cancer. Therefore, while treatment of H. pylori infection is likely to reduce risk for gastric cancer in other populations, analysis of the cost-effectiveness of universal screening and treatment in an otherwise low-risk population is required.

The following NEJM Journal Watch summary explains the study and results in more detail.

John R. Saltzman, MD reviewing Choi IJ et al. N Engl J Med 2020 Jan 30

Risk factors for gastric cancer include infection with H. pylori and a family history of gastric cancer. Having a first-degree relative with gastric cancer is associated with a twofold to threefold increased risk for gastric cancer. So, for people in this high-risk category, does eradication of H. pylori reduce risk for gastric cancer?

To answer this question, investigators from Korea performed a single-center, double-blind, placebo-controlled trial in 1676 patients who had a first-degree relative with gastric cancer and endoscopically documented H. pylori infection. The treatment group received amoxicillin, clarithromycin, and lansoprazole twice daily for 7 days, and eradication was confirmed in 551 of 786 participants (70.1%).

During a median follow-up of 9 years, gastric cancer developed in 10 people (1.2%) in the treatment group compared with 23 people (2.7%) in the placebo group. In patients with successful H. pylori eradication, gastric cancer developed in 5 of 608 (0.8%) compared with 28 of 979 (2.9%) with persistent infection (hazard ratio, 0.27).

Comment: Successful eradication of H. pylori infection reduced the risk for gastric cancer by 73% in first-degree relatives of persons with gastric cancer. As this study was performed in Korea where there is a high prevalence of H. pylori infection, it is not clear if a similar benefit would be seen in other patient populations. H. pylori treatment regimens containing clarithromycin should only be used in patients with no previous history of macrolide exposure who reside in areas where H. pylori clarithromycin resistance is low. Since H. pylori is the only modifiable risk factor for gastric cancer, I would recommend testing for it, eradicating it if present, and documenting successful eradication in persons with a first-degree family member with gastric cancer.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Browse more From Pages to Practice »

Rebecca was a 2016-2017 NEJM Editorial Fellow and is a hospitalist at Massachusetts General Hospital. She graduated from Columbia University College of Physicians and Surgeons in 2013 and completed internal medicine residency at Massachusetts General Hospital in 2016. Her interests include medical education, quality improvement, patient safety, health care delivery innovation, and teaching value in health care.