Hereditary Gastric Cancer Is Linked With Hereditary Breast and Ovarian Cancer.

Background: (), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby infection induces GC development remains unclear. Intermittent injection of the cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between infection, pathogenic variants (PVs), GC and higher GC incidence in HBOC families.

Methods: We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine.

Results: We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of -infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had PVs. Furthermore, expressing wild-type BRCA1/2 in mice (a mouse model of human GC) inhibited GC development. Thus, PVs and infection synergistically increase the risk of GC development.

Conclusion: Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.