A Double Whammy on Gastric Cancer Risk

This editorial discusses a study by Usui et al., which reveals a striking gene-environment interaction between pathogenic germline variants in homologous recombination (HR) genes and Helicobacter pylori infection in elevating gastric cancer risk. The authors explain that individuals with HR gene variants (e.g., BRCA1, BRCA2, PALB2, ATM) who are infected with H. pylori face a markedly increased lifetime risk of gastric cancer (45.5%), compared to noninfected carriers (<5%) or infected noncarriers (14.4%). The findings challenge previous assumptions that gastric cancer lacks a strong hereditary component, showing how DNA damage induced by H. pylori, especially strains expressing the type IV secretion system (T4SS) leads to mutagenic repair in HR-deficient individuals. This editorial underscores the importance of understanding complex gene–environment interactions in cancer development and opens avenues for targeted prevention and surveillance.

This editorial discusses a study by Usui et al., which reveals a striking gene-environment interaction between pathogenic germline variants in homologous recombination (HR) genes and Helicobacter pylori infection in elevating gastric cancer risk. The authors explain that individuals with HR gene variants (e.g., BRCA1, BRCA2, PALB2, ATM) who are infected with H. pylori face a markedly increased lifetime risk of gastric cancer (45.5%), compared to noninfected carriers (<5%) or infected noncarriers (14.4%). The findings challenge previous assumptions that gastric cancer lacks a strong hereditary component, showing how DNA damage induced by H. pylori, especially strains expressing the type IV secretion system (T4SS) leads to mutagenic repair in HR-deficient individuals. This editorial underscores the importance of understanding complex gene–environment interactions in cancer development and opens avenues for targeted prevention and surveillance.