ZNF311 – Cancer

This summary evaluates the association between ZNF311 (HGNC:13847) and cancer (MONDO_0004992). Two major studies provide evidence regarding telomere length regulation as a potential intermediate phenotype with implications for cancer risk. While ZNF311 was identified through genome‑wide association studies, the direct link to cancer predisposition remains tentative. The available data suggest that altered telomere length associated with ZNF311 variants might contribute to pathogenesis, yet the clinical significance for diagnostic testing is not fully established (PMID:23900074).

The genetic evidence arises primarily from a meta‑analysis of three GWAS that included 2,240 individuals with telomere length measurements and replication in over 15,000 healthy controls plus 11,024 breast cancer cases. In that study, ZNF311 reached statistical significance with a Ptrend of less than 7 × 10⁻⁷, suggesting that variation at this locus significantly affects telomere length (PMID:23900074). However, the study emphasized that these TL‐associated variants display little direct evidence for an influence on hormone‑related cancer risk.

A second study in Ataxia‑Telangiectasia families, which included 284 ATM mutation carriers from 103 families, reported that the ZNF311‐tagging SNP rs9257445 was associated with telomere length in heterozygous subjects (PMID:28981872). Although the involvement of ZNF311 in modulating telomere length was evident, there remains minimal segregation data or robust case‑control evidence directly linking ZNF311 variation to cancer risk in these families.

No specific coding variant with complete HGVS nomenclature was detailed in the supplied evidence; thus, no definitive pathogenic variant has been reported for ZNF311 in the context of cancer. Current reports rely on common variant association signals from GWAS arrays rather than rare, highly penetrant mutations.

At the mechanistic level, while ZNF311 appears to influence telomere length—a biological feature implicated in cellular aging and genomic stability—there are no dedicated functional studies demonstrating a direct pathogenic mechanism in cancer development. Functional assays, expression analyses, or animal models directly validating the role of ZNF311 in oncogenesis remain limited.

In summary, the genetic and experimental evidence linking ZNF311 to cancer is currently best classified as Limited. Although ZNF311 variants are reproducibly associated with telomere length modulations, the direct impact on cancer risk is modest and requires further validation to establish robust clinical utility. Key take‑home message: While promising as a marker of altered telomere biology, ZNF311 currently provides only limited actionable evidence for cancer diagnostics and risk assessment.

References

• Human Molecular Genetics • 2013 • A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk PMID:23900074
• Carcinogenesis • 2017 • Telomere length, ATM mutation status and cancer risk in Ataxia-Telangiectasia families PMID:28981872

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