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This summary reviews the association between RCCD1 (HGNC:30457) and breast cancer (MONDO_0007254). Multiple large‐scale meta‑analyses have interrogated the genetic risk factors underlying hormone‑related cancers, and RCCD1 has emerged as a reproducible susceptibility locus in these efforts. The studies combined data from over 112,000 cancer cases and 116,000 controls, providing a robust statistical framework for evaluating genetic associations (PMID:27432226). The integration of diverse cohorts and multi‑ethnic samples strengthens the generalizability of these findings. Such extensive case–control data offer compelling evidence for the gene’s involvement in breast cancer. This body of evidence is of high value for both diagnostic decision‑making and commercial genetic testing.
The clinical validity of the RCCD1–breast cancer association is rated as Strong. Multiple independent genome‑wide association studies (GWAS) have demonstrated significant signals at the RCCD1 locus, with replication in diverse cohorts (PMID:27432226; PMID:28362817; PMID:38590415). These studies, which include large meta‑analyses and trans‑ethnic approaches, collectively reflect thousands of affected individuals. The reproducibility and statistical strength of these findings justify a high classification by ClinGen standards. In addition, the observed associations have been consistent across independent datasets, further reinforcing the reliability of this association.
Genetic evidence for RCCD1 is underpinned by multiple independent association signals identified via robust GWAS approaches. Although explicit coding variants in RCCD1 were not reported with full HGVS detail in the abstracts, the aggregated data clearly implicate RCCD1 through significant single‑nucleotide polymorphism signals. The expression quantitative trait locus (eQTL) analyses provided in these studies show that altered RCCD1 expression levels are associated with breast cancer risk, adding a functional component to the genetic association. Thus, the weight of genetic evidence is solid and meets the criteria for a Strong rating, as it is supported by high case counts and consistency across independent cohorts.
While a specific HGVS‐formatted coding variant was not directly provided in the multi‑patient studies, the absence of a designated variant does not diminish the genetic association signal. To date, no coding alteration meeting the full criteria for HGVS nomenclature has been robustly reported in the literature for RCCD1 in the context of breast cancer. Future studies may yield such precise variant information; however, the current association is based on statistical and expression data rather than on single‐variant causality.
Functional evidence for the RCCD1–breast cancer association remains more limited compared to the genetic data. Although dedicated in vitro or in vivo functional assays for RCCD1 were not detailed in the provided evidence, integrative multi‑omics analyses suggest that RCCD1 may play a regulatory role in breast tissue biology. These studies indicate that differences in RCCD1 expression correlate with altered disease risk, implying a potential mechanism of pathogenicity that may involve dysregulation of cell cycle or transcriptional control. No significant conflicting evidence was noted, and the overall data support a contributory role for RCCD1 in disease risk.
In conclusion, the integration of large‑scale meta‑analyses, replication across diverse cohorts, and transcriptomic associations collectively support a strong link between RCCD1 and breast cancer. This association, rated as Strong by ClinGen criteria, underscores the clinical utility of RCCD1 in risk assessment and opens avenues for its incorporation into diagnostic and commercial genetic testing panels. The key take‑home message is that RCCD1 represents a robust genetic marker for breast cancer susceptibility, providing a valuable tool for personalized risk stratification and future therapeutic targeting.
Gene–Disease AssociationStrongMeta‑analyses including over 112,349 breast cancer cases (PMID:27432226) and replication in independent cohorts (PMID:28362817; PMID:38590415) support a robust association. Genetic EvidenceStrongMultiple independent GWAS signals and significant eQTL associations implicate RCCD1 with strong statistical support across large cohorts. Functional EvidenceLimitedAlthough direct functional assays are not reported, multi‑omics analyses suggest RCCD1 may play a regulatory role in breast tissue biology consistent with the disease phenotype. |