Eradicating Infection to Reduce Gastric Cancer Risk

Eradication treatment of Helicobacter pylori (H. pylori) infection reduced the risk for gastric cancer among those with a first-degree relative with the disease, according to study findings published in The New England Journal of Medicine.

H. pylori infection, which occurs when this type of bacteria infects the stomach, may be present in more than half the people in the world. Often contracted in childhood, the infection can be a result of living in crowded conditions, living without a reliable supply of clean water, living in a developing country or living with someone who has H. pylori infection.

Previous studies have shown an association between the infection and gastric cancer. Moreover, the infection coupled with a family history of gastric cancer is the main risk factors for the disease.

“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 H. pylori in the environment and genetic features that may affect immune responses to H. pylori infection,” the researchers explained. “Family members of patients with gastric cancer have higher rates of H. pylori infection than persons in the general population, and the precancerous histologic changes in the gastric mucosa are more severe in these persons.”

However, it is unknown whether treatment of H. pylori can reduce the risk of gastric cancer in those with a family history of the disease in first-degree relatives.

In a single-center, double-blind, placebo-controlled trial, the researchers aimed to determine whether treatment of the infection reduces the risk of gastric cancer in 3,100 first-degree relatives of patients with gastric cancer, compared to 1,838 randomly assigned participants with H. pylori infection to receive either eradication therapy or placebo.

Eradication therapy included 30 mg of lansoprazole (which decreases the amount of acid produced in the stomach), 1,000 mg of amoxicillin (a penicillin antibiotic that fights bacteria) and 500 mg of clarithromycin (a macrolide antibiotic that fights bacteria in the body), each taken twice daily for seven days.

Patients were screened from November 2004 to December 2011. The primary analysis of the study included 832 patients in the treatment group and 844 participants in the placebo group.

After a median follow-up of 9.2 years, 10 (1.2%) patients in the treatment group and 23 (2.7%) participants in the placebo group developed gastric cancer, reducing the risk of developing the disease by 55% in those with a first-degree relative of a patient with gastric cancer.

Among the 33 individuals who developed gastric cancer, 30 (90.9%) had stage 1 disease and three (9.1%) had stage 2.

H. pylori eradication status was evaluated in 1,587 participants during the follow-up period, including 786 in the treatment arm and 801 in the placebo arm. Eradication was confirmed in 551 (70/1%) and 57 (7.1%) of participants, respectively.

Of the 33 cases of gastric cancer, the disease developed in 28 (2.9%) of those with persistent infection and five (0.8%) of the participants in whom the infection was eradicated, reducing the risk for gastric cancer by 73% among those with eradicated infection as compared with persistent infection.

Of the 10 patients in the treatment group, five developed gastric cancer and had persistent H. pylori infection and five developed the disease with confirmed eradication.

After a median duration of 10.2 years of follow-up, no difference was seen in overall survival between arms.

Side effects, including taste alteration, nausea, diarrhea and abdominal pain, were mild and more common in the treatment group, compared with the placebo group (53.0% vs. 19.1%).

“Our data emphasize that eradication success should be confirmed, as the ‘test—treat–test’ approach recommends,” the researchers concluded.