FCGRT and Breast Cancer

The current evidence for the association between FCGRT (HGNC:3621) and breast cancer (MONDO:0007254) is limited. In one familial case report of multiple primary cancers, FCGRT was identified alongside four other genes in a candidate gene panel from two affected siblings, one of whom had breast cancer (PMID:27900359). However, no FCGRT‑specific variant meeting the strict HGVS criteria was reported and segregation data for FCGRT remain uninformative.

Extensive functional studies have characterized the biochemical role of the neonatal Fc receptor encoded by FCGRT in IgG binding, transcytosis, and serum homeostasis (PMID:8700168; PMID:9036967; PMID:12391234; PMID:12972260; PMID:15644205; PMID:17135257). While these data robustly support FCGRT’s canonical functions, they do not directly establish its role in breast cancer pathogenesis. Taken together, the genetic evidence is modest and limited by the lack of confirmed pathogenic FCGRT variants and extensive segregation, despite the wealth of functional data on FcRn biology.

Key Take‑home: Although FCGRT remains a compelling candidate given its central role in IgG regulation, additional replicated genetic and mechanistic studies are needed to clarify its clinical utility in breast cancer diagnostics.

References

• Cold Spring Harbor molecular case studies • 2016 • Homozygous inactivation of CHEK2 is linked to a familial case of multiple primary lung cancer with accompanying cancers in other organs PMID:27900359
• Molecular immunology • 1996 • The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I‑related receptor, FcRn PMID:8700168
• Journal of immunology • 1997 • Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1 PMID:9036967
• Journal of immunology • 2002 • Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences PMID:12391234
• Journal of molecular biology • 2003 • Generation of mutated variants of the human form of the MHC class I‑related receptor, FcRn, with increased affinity for mouse immunoglobulin G PMID:12972260
• Journal of molecular biology • 2005 • Conferring the binding properties of the mouse MHC class I‑related receptor, FcRn, onto the human ortholog by sequential rounds of site‑directed mutagenesis PMID:15644205
• The Journal of biological chemistry • 2007 • Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor PMID:17135257

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