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The association between NCOA7 (HGNC:21081) and breast cancer (MONDO:0007254) has been evaluated in multiple genetic studies. One investigation evaluating the missense SNP rs1567 in NCOA7 in 305 sporadic breast cancer cases and 346 controls did not detect any significant difference in allele frequencies (PMID:22740868). This negative study raises questions about the role of this individual variant in breast cancer risk.
Conversely, a multistage association study assessed a haplotype spanning the initial protein-coding exon of NCOA7 in three independent cohorts (NBC with 510 cases and 988 controls, CGEMS with 1145 cases and 1142 controls, and CBCS with 1552 cases and 1185 controls (PMID:21610108). This study demonstrated a consistent protective effect with an overall odds ratio of approximately 0.75, suggesting that genetic variation at this locus may be inversely associated with breast cancer risk.
Genetically, the evidence is complicated by the discordant findings. While the protective haplotype offers a statistically significant signal across large cohorts, the absence of association for SNP rs1567 and the lack of segregation data in familial settings preclude a higher classification of gene–disease validity.
Functional assessments provide modest supporting evidence. Preliminary data indicate that NCOA7 encodes a nuclear receptor coactivator expressed in the mammary gland and capable of interacting with the estrogen receptor. This mechanistic insight is consistent with a role in estrogen signaling; however, the absence of in vivo models or rescue experiments further limits the functional evidence available.
In summary, although the multi‐patient haplotype study suggests a protective genetic effect for NCOA7 variants in breast cancer, the conflicting findings and paucity of segregation and robust functional data result in an overall classification of Limited evidence for this gene–disease association. Clinicians and researchers should consider these nuances in genetic risk assessments, while additional studies are warranted to clarify the clinical utility of NCOA7 variants.
Key Take‑home sentence: Emerging evidence indicates that NCOA7 variation may modulate breast cancer risk, but further investigation is needed to support clinical diagnostic use.
Gene–Disease AssociationLimitedOne study evaluating SNP rs1567 did not show an association (PMID:22740868), while a large multi‐cohort haplotype analysis demonstrated a significant protective effect (PMID:21610108). The limited segregation and lack of extensive functional assays constrain the overall validity. Genetic EvidenceLimitedThe genetic evidence is primarily based on population case–control studies with conflicting results. Although a protective haplotype was consistently observed, a lack of familial segregation data limits the genetic evidence strength. Functional EvidenceLimitedPreliminary functional data indicate that NCOA7 interacts with the estrogen receptor in breast tissue, suggesting a plausible mechanism. However, the absence of in vivo models or rescue experiments restricts the functional evidence level. |