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Review
. 2022 Dec 1;14(23):5953.
doi: 10.3390/cancers14235953.

Gastric Cancer Risk and Pathogenesis in BRCA1 and BRCA2 Carriers

Kole H Buckley  1 , Blake A Niccum  1 , Kara N Maxwell  2 , Bryson W Katona  1
Affiliations
Review

Gastric Cancer Risk and Pathogenesis in BRCA1 and BRCA2 Carriers

Kole H Buckley et al. Cancers (Basel). .

Abstract

Carriers of a pathogenic germline variant (PV) in BRCA1 or BRCA2 are at increased risk for a number of malignancies, including breast, ovarian, pancreatic, and prostate cancer. In this review, we discuss emerging evidence that BRCA2 PV carriers, and likely also BRCA1 PV carriers, are also at increased risk for gastric cancer (GC), highlighting that GC may be part of the BRCA1/2 cancer risk spectrum. While the pathogenesis of GC among BRCA1/2 PV carriers remains unclear, increasing evidence reveals that GCs are often enriched with mutations in homologous recombination-associated genes such as BRCA1/2, 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 BRCA1/2 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 BRCA1/2 PVs and development of GC as well as to determine how GC risk management should be factored into the clinical care of BRCA1/2 carriers.

Keywords: DNA damage; breast cancer susceptibility gene; hereditary breast and ovarian cancer syndrome; pathogenic germline variants; stomach cancer.

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Conflict of interest statement

The authors declare no relevant conflict of interest. BWK discloses research support from Epigenomics, Freenome, Guardant Health, Immunovia, Janssen Pharmaceuticals, and Universal Diagnostics, as well as non-funded research collaborations with Ambry, Myriad, GeneDx, and Invitae.

Figures

Figure 1
Figure 1
Cancer Risks Associated with BRCA1 and BRCA2 Germline Pathogenic Variants.
See this image and copyright information in PMC

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