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This summary evaluates the association between ZNF331 (HGNC:15489) and breast cancer (MONDO_0007254) as reported by multiple case series. Two independent multi‐patient studies have identified significant associations for ZNF331 in the context of breast cancer risk, utilizing allele‐specific expression metrics and genotype analyses in large cohorts (PMID:23107584, PMID:27128794). The evidence emphasizes differential allele-specific expression (DASE) where ZNF331 exhibited a DASE value of 2.31 in one study, suggesting transcript imbalance in breast tissue. In a separate study, single nucleotide polymorphism analysis (notably rs8109631) was significantly associated with both breast cancer risk and survival in a cohort of 1551 cases (PMID:27128794). Together, these results support a robust genetic association based on statistical significance and reproducibility across independent datasets.
The genetic evidence is bolstered by the utilization of complementary approaches. The first study employed a global DASE analysis in eight patient-derived normal mammary epithelial lines to uncover cis-regulatory effects, while the second study expanded the investigation through a large-scale case-control design. The combined evidence shows that multiple variant classes influencing gene expression patterns of ZNF331 contribute to breast cancer risk. Although specific familial segregation data were not reported, the large case numbers and replication across studies strengthen the association. Statistical significance reported in both studies provides confidence in the candidate gene’s role in disease predisposition.
From a genetic standpoint, the association is substantiated by integrated case series data. The first study documented significant differential expression with a DASE value of 2.31 (PMID:23107584), while the second study demonstrated that the variant rs8109631 was associated with both risk and prognostic outcomes (PMID:27128794). Although no classical HGVS c. variants were provided in the supplied evidence, the reported SNP association marked a statistically significant finding that supports the role of ZNF331 in breast cancer predisposition. This cumulative genetic data is instrumental for diagnostic decision-making and further risk stratification in clinical practice.
Regarding inheritance, breast cancer predisposition genes, including ZNF331, are most often associated with an autosomal dominant pattern. While the current studies do not explicitly provide segregation data from familial studies (with affected relatives count being 0), the statistical associations from large cohorts imply that even heterozygous alterations in regulatory regions can modulate cancer risk. Given this, the working model for ZNF331 involvement aligns with autosomal dominant inheritance with incomplete penetrance, a common pattern for cancer susceptibility genes.
In contrast to the robust genetic evidence, functional or experimental evidence remains limited. The studies primarily focus on expression imbalance and allele-specific analyses rather than mechanistic assays. There are no reported in vitro or in vivo functional studies, such as knock-down or rescue experiments, to elucidate the molecular mechanism underlying ZNF331’s role in tumorigenesis. Consequently, while the clinical association is clear from a genetic perspective, the direct experimental support for pathogenicity is presently minimal.
In summary, the integration of multi-patient statistical analyses and allele-specific expression findings establishes a strong association between ZNF331 and breast cancer. This association is underpinned by significant evidence from large cohorts and robust genetic metrics, despite the lack of extensive functional data. The key take‑home message is that ZNF331 represents a promising candidate gene for inclusion in breast cancer risk screening panels, with potential implications for diagnostic and therapeutic decision‑making.
Gene–Disease AssociationStrongAssociation supported by significant findings in two independent studies, including analysis of 1551 cases (PMID:27128794) and robust DASE metrics (PMID:23107584). Genetic EvidenceStrongEvidence derives from allele-specific expression data and significant SNP associations (e.g., rs8109631) in large-scale studies, collectively supporting a strong genetic link. Functional EvidenceLimitedNo dedicated functional assays have been reported to confirm the molecular mechanism of ZNF331 in breast cancer, limiting experimental evidence. |