Genetic variants plus "H. Pylori" risk for gastric cancer

Medislove Editorial Team 8 months ago 3 m

An international team of researchers located at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan discovered that people who carry certain genetic risk factors for gastric cancer have a higher risk of developing this disease if they have also been infected by the bacterium Helicobacter pylori. The finding, published in The New England Journal of Medicine, could contribute to the development of a genomic medicine tailored to treat specifically this tumor, according to the authors.

Stomach cancer is the fourth leading cause of cancer death worldwide and its potential development is influenced by both environmental and genetic risk factors. Environmentally, H. pylori infection increases the risk of stomach cancer. Because the presence of H. pylori in East Asia is high, the incidence of stomach cancer is higher in countries such as Japan, for example.

Study in Japanese population

Tokyo Capital of Japan (Japanese population).

From a genetic point of view, certain variants are known to be associated with the risk of disease. Thus, people who carry a certain inherited pathogenic variant of the CDH1 gene have an increased risk of gastric cancer, for example.

Testing for the presence of pathogenic variants is now another of the various measures being taken for cancer prevention, surveillance and treatment selection. However, large-scale case-control studies are still lacking. Moreover, the data from those that have been conducted have not yet assessed how the risk of stomach cancer changes when pathogenic variants interact with environmental factors such as H. pylori. Therefore, it is also unclear what actual clinical measures could be undertaken.

To address this problem, the research team analyzed the risk of gastric cancer in a large-scale case-control study in a Japanese population, considering whether they were carriers of pathogenic variants and whether they had been infected with H. pylori.

Using a method for genomic analysis originally developed at RIKEN, the joint team led by Yukihide Momozawa of the RIKEN IMS Genotyping Development Laboratory and Keitaro Matsuo of the Division of Cancer Epidemiology and Prevention at the Aichi Cancer Center in Japan analyzed DNA samples from more than 11,000 patients with gastric cancer and 44,000 people without cancer for 27 genes associated with tumor inheritance. Then, they studied the interaction between pathogenic variants in the nine genes and each patient's history of H. pylori infection.

The first finding was that the risk of gastric cancer was significantly higher when a pathogenic variant was combined with H. pylori infection than when either factor was present alone. Of the nine genes on which the study focused, four were of particular interest because they encode proteins that normally help repair damaged DNA.

Yoshiaki Usui, coordinator of the research, believes that these pathogenic variants exacerbate the damage caused by H. pylori infection. "Infection with this bacterium leads to tumor development because it promotes DNA double-strand breaks and destabilizes the DNA of stomach cells. The combination of this phenomenon with the presence of genetic variants that prevent normal repair of the damage appears to substantially increase the risk of gastric cancer."

Since the prevalence of H. pylori infection is high and eradication has proven difficult, detection of pathogenic variants may help determine who should be prioritized for interventions. Overall, reducing the risk of stomach cancer by testing for H. pylori infection and eradicating it remains a high priority for the medical profession, regardless of whether they carry the pathogenic variants.

Prevention and eradication

"For clinical practice, we will have to determine to what extent H. pylori eradication actually has a preventive effect or when eradication should be considered," Matsuo notes.

For this professional, the information obtained will contribute to the renewal of medical practice guidelines on gastric cancer and pathogenic variants. "It is expected to contribute to the establishment of a tailor-made genomic medicine system, including improved diagnostic accuracy, the development of therapies targeting the causative genes, and the most appropriate methods and preventive measures to reduce gastric cancer cases," says Momozawa.