CCDC91 and Breast Cancer

Recent large-scale association studies have implicated CCDC91 (HGNC:24855) in conferring susceptibility to breast cancer (MONDO_0007254). Two independent studies identified multiple association signals at the 12p11 locus, demonstrating robust associations in diverse populations. In one study, fine‐scale mapping in over 48,000 cases and 43,000 controls of European descent, as well as additional cohorts in East Asian and African populations, revealed four independent signals with highly significant odds ratios (PMID:27459855). The second study, involving a meta‐analysis of prospective cohorts and Mendelian randomization analyses with over 46,000 cases, further supported the association of common regulatory variants near CCDC91 with breast cancer risk (PMID:26296642).

The genetic evidence is bolstered by the discovery of independent signals across multiple case series and populations. Although specific coding variants in the form of HGVS nomenclature were not documented in these reports, the studies consistently indicate that noncoding regulatory variation near CCDC91 contributes to disease risk. Segregation analysis in affected families was not detailed in these large-scale studies.

From a mechanistic perspective, while candidate regulatory variants have been identified, direct functional studies linking CCDC91 to the pathogenesis of breast cancer are currently limited. This contrasts with functional studies in other conditions, underscoring the need for future experimental work to delineate the biological pathways involved. In short, the experimental evidence remains constrained and does not yet fully clarify the mechanism of pathogenicity in the context of breast cancer.

In summary, the integration of robust genetic data from large consortia with suggestive but limited experimental evidence supports a strong overall gene-disease association between CCDC91 and breast cancer. The independent replication of association signals across varied populations provides compelling evidence for its clinical relevance. Nonetheless, additional functional validation is warranted to reinforce these findings.

The available evidence from multiple studies exceeds the standard scoring thresholds and emphasizes the clinical utility of genetic testing and risk stratification in breast cancer. Key take-home: CCDC91 represents a strong candidate gene for breast cancer susceptibility and may serve as an important biomarker in diagnostic decision-making and precision medicine.

References

• Breast Cancer Research : BCR • 2016 • Identification of independent association signals and putative functional variants for breast cancer risk through fine‑scale mapping of the 12p11 locus PMID:27459855
• Journal of the National Cancer Institute • 2015 • Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization PMID:26296642

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