Gastric Cancer Risk and Pathogenesis in and Carriers.

Carriers of a pathogenic germline variant (PV) in or are at increased risk for a number of malignancies, including breast, ovarian, pancreatic, and prostate cancer. In this review, we discuss emerging evidence that PV carriers, and likely also PV carriers, are also at increased risk for gastric cancer (GC), highlighting that GC may be part of the cancer risk spectrum. While the pathogenesis of GC among PV carriers remains unclear, increasing evidence reveals that GCs are often enriched with mutations in homologous recombination-associated genes such as , and that GC prognosis and response to certain therapies can depend on BRCA1/2 expression. Given the strength of data published to date, a risk management strategy for GC among PV carriers is needed, and herein we also propose a potential strategy for GC risk management in this population. Moving forward, further study is clearly warranted to define the mechanistic relationship between PVs and development of GC as well as to determine how GC risk management should be factored into the clinical care of carriers.