FZD7 and Classic Familial Adenomatous Polyposis

FZD7 has been evaluated as a candidate gene in familial studies of colorectal cancer predisposition, including cases classified as classic familial adenomatous polyposis. Despite its biological plausibility given its role in the Wnt signaling pathway, targeted sequencing in familial serrated neoplasia cohorts failed to identify any segregating pathogenic variants in FZD7 (PMID:21165777).

In multi‐patient studies, FZD7 was included among several candidate genes, yet no causative variants were detected in probands with classic familial adenomatous polyposis. The absence of supportive genetic alterations in affected individuals and their relatives limits the strength of the genetic evidence for this gene–disease relationship (PMID:21165777).

Segregation analyses within the studied families demonstrated no additional affected relatives with FZD7 variants, further tempering the potential clinical relevance of FZD7 in this context. As a result, the overall genetic evidence is categorized as limited.

Classic familial adenomatous polyposis is typically transmitted in an autosomal dominant manner. Although FZD7 was evaluated under this model, the lack of identified variants along with the negative segregation findings compromises its utility for diagnostic decision‑making in this disorder.

Functional assessments of FZD7 in other neoplastic settings, such as colorectal cancer, have demonstrated its capacity to modulate the Wnt signaling pathway, a critical driver in many tumor types. However, while these experimental insights are supportive of a role in oncogenesis, they have not been directly linked to the familial adenomatous polyposis phenotype (PMID:18592008).

In summary, the current evidence supports only a limited association between FZD7 and classic familial adenomatous polyposis. Although functional studies provide moderate support for its involvement in cancer biology, the absence of causative and segregating variants in familial cases limits its clinical utility. Further research is needed to clarify whether FZD7 may contribute to a subset of cases or act as a modifier, but at present, its application in diagnostic and commercial contexts remains constrained.

References

• Familial cancer • 2011 • Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome) PMID:21165777
• Neoplasia (New York, N.Y.) • 2008 • Frizzled-7 as a potential therapeutic target in colorectal cancer PMID:18592008

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