BRCA mutations and gastrointestinal cancers: When to expect the unexpected?

Area of Science:

• Oncology
• Genetics
• Gastroenterology

Background:

• BRCA1/2 pathogenic variants are established risk factors for breast and ovarian cancers.
• The role of BRCA1/2 variants in gastrointestinal (GI) malignancies, including colorectal cancer (CRC), gastric cancer, and esophageal cancer (OeC), is less understood.

Purpose of the Study:

• To review and summarize existing evidence on the association between BRCA1/2 pathogenic variants and GI cancers.
• To evaluate BRCA1/2 variants as potential risk, prognostic, or predictive factors in CRC, gastric cancer, and OeC.

Main Methods:

• Systematic literature search of PubMed, Google Scholar, and ScienceDirect databases.
• Inclusion of studies assessing BRCA1/2 pathogenic variants in relation to GI malignancies.

Main Results:

• Evidence suggests BRCA1/2 variants may confer risk for CRC, gastric cancer, and OeC, with distinct patterns: BRCA1 is more frequent in CRC, while BRCA2 is associated with gastric and OeC.
• BRCA1/2 mutations are linked to early-onset GI cancers.
• A potential positive prognostic role for these mutations is suggested, though predictive value assessment is limited due to common platinum-based chemotherapy use.

Conclusions:

• BRCA1/2 variants represent a potential risk factor for specific GI cancers.
• Further research and clinical trials, including those investigating poly (ADP-ribose) polymerase inhibitors, are warranted to clarify the role and therapeutic implications of BRCA1/2 variants in GI oncology.