木瓜直播

The combined effect of certain germline pathogenic variants and Helicobacter pylori infection were linked with large increases in gastric cancer risk, according to results from a Japanese study.

By age 85, the cumulative risk for gastric cancer in people with H. pylori infection was three times higher among carriers of pathogenic variants in homologous-recombination genes (ATM, BRCA1/2, PALB2), at 45.5% versus 14.4% for noncarriers, reported Yukihide Momozawa, DVM, PhD, of the RIKEN Center for Integrative 木瓜直播 Sciences in Yokohama, Japan, and colleagues.

Meanwhile, people without an H. pylori infection had a lifetime gastric cancer risk of less than 5%, regardless of their carrier status.

"Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important," wrote Momozawa and colleagues in the .

When combined with H. pylori infection, even a larger subset of pathogenic variants -- also including APC, CDH1, MLH1, MSH2/6 -- demonstrated a "significant additive interaction with respect to the risk of gastric cancer," the group wrote.

In an , entitled "A Double Whammy on Gastric Cancer Risk," Anne Müller, PhD, and Jiazhuo He, MD, both of the University of Zurich in Switzerland, wrote that until now, hereditary forms of gastric cancer were believed to be limited and restricted to a small percentage of CDH1-mutant cases.

Therefore, the results of the study "imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed and suggests that DNA damage induced by H. pylori, if repaired incorrectly or not at all, is a major driver of gastric carcinogenesis," they said.

Furthermore, Müller and He observed, the study shows "that it takes an enormous effort and access to well annotated cohorts of tens of thousands of patients and healthy controls to unravel complex gene-environment interactions and that this effort, combined with careful well-resourced biobanking, pays off."

For their study, Momozawa's team included a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan (BBJ), as well as a sample from Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) that included 1,433 patients with newly diagnosed gastric cancer and 5,997 controls without cancer, all of whom had an H. pylori infection status indicated.

Median age was 69 years among the BBJ patients with gastric cancer (and 64 years for controls) and 62 years among the HERPACC patients with gastric cancer (55 years for these controls). Men accounted for about 75% of the patients in the BBJ and HERPACC samples, and 53.1% and 51.1% of the two control groups, respectively.

In all, 27 cancer-predisposing genes were evaluated in order to identify the nine gastric cancer risk genes. The prevalence of pathogenic-variant carriers among patients with gastric cancer was similar in the HERPACC and BBJ samples (2.5% and 2.7%, respectively), and 88.9% of carriers and 86.4% of noncarriers had evidence of H. pylori infection. Carriers of variants in BRCA1, BRCA2, and ATM accounted for more than half the variant carriers in any age group.

Researchers found interactions between H. pylori infection and pathogenic variants in all nine genes with respect to the risk of gastric cancer, with a relative excess risk due to the interaction of 14.22 (95% CI 2.50-25.93, P=0.02), and in the four homologous-recombination genes (ATM, BRCA1/2, PALB2), with a relative excess risk of 16.01 (95% CI 2.22-29.81, P=0.02).

Momozawa and colleagues suggested that a mechanism underlying this excess risk "is genome instability caused by H. pylori infection that contributes to gastric carcinogenesis," and hypothesized that the "gastric carcinogenesis-related DNA damage due to H. pylori infection is enhanced in persons with a reduced DNA damage-repair capacity due to damaging variants in the homologous-recombination genes."

Comment