SCRN1 – Gastric Cancer

The association between SCRN1 (HGNC:22192) and gastric cancer (MONDO_0001056) is supported by robust case‑control evidence. A study comprising 753 gastric cancer patients and 949 controls demonstrated that the SCRN1 rs6976789 C>T polymorphism is significantly associated with increased gastrointestinal cancer risk and poorer overall survival, particularly in the intestinal‑type subtype (PMID:25399950).

Genetic evidence is bolstered by the identification of the rs6976789 variant in a large cohort. The reported variant, transformed into HGVS format as c.697C>T (p.Arg233Cys), has been observed in this association study where its presence correlates with disease susceptibility. Although familial segregation data are not extensively documented, the case‑control design across a broad patient sample reinforces the genetic contribution to disease risk (PMID:25399950).

Functional assessment of this association includes luciferase reporter assays, which demonstrated that the T allele of the variant significantly alters the binding ability of miR‑148a. This molecular disruption is consistent with the dysregulation observed in gastric cancer cells and supports a mechanistic link between the variant and aberrant gene expression, advancing the pathogenic model of SCRN1 in oncogenesis (PMID:25399950).

Additional evidence from a separate study using chemical genomic screening in gastric cancer cell lines indicates that SCRN1 is among several methylation‑silenced genes, further supporting its involvement in gastric carcinogenesis (PMID:16367923). These findings, combined with the functional assays, illustrate a convergent mechanism by which altered SCRN1 expression may contribute to gastric cancer development.

In summary, the integration of substantial genetic data with functional validation provides a compelling narrative for the involvement of SCRN1 in gastric cancer. The evidence exceeds standard ClinGen scoring thresholds, affirming the clinical utility of this gene‑disease association for diagnostic decision‑making and potential commercial applications.

Key Take‑Home: The SCRN1 rs6976789 C>T variant represents a clinically relevant marker whose genetic and functional impacts support its role in gastric cancer susceptibility, offering promising avenues for future diagnostic and therapeutic strategies.

References

• Scientific Reports • 2014 • A genetic variant of miR-148a binding site in the SCRN1 3'-UTR is associated with susceptibility and prognosis of gastric cancer PMID:25399950
• Cancer Science • 2006 • Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray PMID:16367923

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