In a Japanese study reported in The New England Journal of Medicine, Usui et al found that Helicobacter pylori infection affected the risk of gastric cancer in patients with predisposing germline pathogenic variants, including variants in homologous recombination genes.
As stated by the investigators, “H pylori infection is a well-known risk factor for gastric cancer. However, the contribution of germline pathogenic variants in cancer-predisposing genes and their effect, when combined with H pylori infection, on the risk of gastric cancer has not been widely evaluated.”
The study assessed associations between germline pathogenic variants in 27 cancer-predisposing genes and risk of gastric cancer in a cohort of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. The combined effect of the presence of pathogenic variants and H pylori infection status on the risk of gastric cancer was assessed in 1,433 patients with gastric cancer and 5,997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).
Germline pathogenic variants in nine genes were associated with a significantly increased risk of gastric cancer: APC (odds ratio [OR] = 14.17), ATM (OR = 5.50), BRCA1 (OR = 4.81), BRCA2 (OR = 5.08), CDH1 (OR = 8.04), MLH1 (OR = 14.45), MSH2 (OR = 4.85), MSH6 (OR = 3.48), and PALB2 (OR = 3.71).
In the HERPACC cohort, among carriers of any of the nine pathogenic variants, odds ratios for gastric cancer were 1.27 among H pylori–negative patients and 20.25 among H pylori–positive patients. The relative excess risk due to the interaction of pathogenic variants and H pylori–positive status was 14.22 (95% confidence interval [CI] = 2.50–25.93, P = .02).
In the HERPACC cohort, among carriers of pathogenic variants in the homologous recombination genes ATM, BRCA1, BRCA2, and PALB2, odds ratios for gastric cancer were 1.68 among H pylori–negative patients and 22.45 among H pylori–positive patients. The relative excess risk due to the interaction of pathogenic variants and H pylori–positive status was 16.01 (95% CI = 2.22–29.81, P = .02).
The cumulative risk of gastric cancer by 85 years of age was 45.5% (95% CI = 20.7%–62.6%) among pathogenic variant carriers with H pylori infection vs 14.4% (95% CI = 12.2%–16.6%) among noncarriers with H pylori infection.
The investigators concluded, “H pylori infection modified the risk of gastric cancer associated with germline pathogenic variants in homologous recombination genes.”
Yukihide Momozawa, DVM, PhD, of the Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the Japan Agency for Medical Research and Development and others. For full disclosures of the study authors, visit nejm.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.