BARD1 – Hereditary Nonpolyposis Colon Cancer

BARD1 has been evaluated as a candidate predisposition gene in hereditary nonpolyposis colorectal cancer (HNPCC). In a panel sequencing study of 849 unrelated probands with suspected hereditary cancer predisposition, a single truncating BARD1 variant was observed, with no significant enrichment compared to controls and no evidence of segregation in affected relatives (PMID:33099839).

Functional analyses in colorectal carcinoma tissues reveal dysregulated BARD1 expression: full-length BARD1 protein levels predict clinical outcome, while oncogenic BARD1 isoforms lacking the RING domain are upregulated in tumors and correlate with advanced stage and poor prognosis (PMID:21693656; PMID:22814582). Although these data demonstrate a role for BARD1 in colonic epithelial biology and tumor progression, there is no direct evidence supporting germline BARD1 variants as causative for HNPCC.

Key take-home: Current evidence is insufficient to implicate BARD1 as a hereditary nonpolyposis colorectal cancer gene, and routine clinical testing of BARD1 for HNPCC is not supported.

References

• Genes, Chromosomes & Cancer • 2021 • Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition. PMID:33099839
• Clinical Cancer Research • 2011 • BARD1 expression predicts outcome in colon cancer. PMID:21693656
• British Journal of Cancer • 2012 • Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome. PMID:22814582

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