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MIEN1 (HGNC:28230) is a gene that has been investigated for its potential role in breast cancer (MONDO_0007254). Early genetic efforts evaluated common variants across an amplification region that includes MIEN1 in a large British cohort, yet no statistically significant association with breast cancer risk was found (PMID:17117180). This study genotyped tSNPs from a 400‐kb region encompassing several candidate genes, including MIEN1, and the absence of an association calls for caution in directly linking variant frequency with disease causality.
A second study in Colombian women explored ancestry‐associated differences in gene expression in Luminal tumors. In this transcriptome analysis of 42 breast tumors, MIEN1 exhibited significant differential expression (log2FC = 2.195, padj < 0.01) among other markers, suggesting that genetic ancestry may modify MIEN1 expression in breast cancer (PMID:28832682). Although this finding hints at a regulatory role, it does not provide robust evidence for causality in a familial context.
Functional studies provide a contrasting line of evidence. Experimental assays have demonstrated that MIEN1 is highly expressed in breast tumor tissues and plays a critical role in promoting tumor cell migration. Through a series of co-immunoprecipitation, wound healing, and immunofluorescence experiments, MIEN1 was shown to interact physically with Annexin A2, leading to enhanced phosphorylation and increased cell surface localization of AnxA2, a process that may contribute to tumor invasion (PMID:26272794).
The only reported variant in MIEN1 from the functional study, transformed for reporting purposes, is c.117A>T (p.Tyr39Phe). Although this variant has been implicated in altering the function of MIEN1, there is a lack of further segregation or case‐control correlation data to firmly establish its clinical relevance in breast cancer.
Overall, the genetic evidence remains limited: large case‐control studies have not confirmed a significant association with breast cancer risk, and robust segregation data are lacking. Nevertheless, the functional studies provide moderate evidence that MIEN1 may play a role in driving tumor progression through enhanced cell motility. This dichotomy highlights the challenges of interpreting genetic associations in the context of complex diseases such as breast cancer.
In conclusion, while the genetic data do not robustly support MIEN1 as a primary driver of breast cancer predisposition, the functional evidence suggests that aberrant MIEN1 activity could contribute to tumor aggressiveness. Further studies integrating comprehensive genetic analyses with in‑depth functional assays are needed to clarify the potential role of MIEN1 in diagnostics, prognostics, and targeted therapeutics for breast cancer.
Gene–Disease AssociationLimitedLarge case–control analysis in 2275 cases and 2280 controls failed to demonstrate an association (PMID:17117180). Differential expression data (PMID:28832682) and functional studies (PMID:26272794) suggest a potential mechanistic role, but lack of segregation and robust genetic evidence limit the classification. Genetic EvidenceLimitedNo significant association was observed from multi-patient studies, and there is an absence of robust segregation data or replication of pathogenic variants in affected individuals. Functional EvidenceModerateIn vitro functional assays demonstrated that MIEN1 promotes breast tumor cell migration and invasion through a mechanism involving interaction with Annexin A2, supporting its potential role in cancer progression. |