S100A14 – Esophageal Squamous Cell Carcinoma

S100A14 has been implicated in the susceptibility to esophageal squamous cell carcinoma. Two independent case‑control studies in Chinese populations have highlighted significant associations between S100A14 variants and ESCC risk. In one study, 629 ESCC patients and 686 controls were evaluated, demonstrating that the rs11548103 G>A polymorphism (when present as the GA or AA genotype) conveyed a decreased risk of developing ESCC (PMID:29156846).

Another study, incorporating 1,021 ESCC cases and 1,253 control subjects, identified four single nucleotide polymorphisms at the S100A14 locus. Among these, the c.461G>A (p.Arg154His) variant was reported as functionally impactful, as it diminishes a P53‑binding site. This biochemical alteration is associated with reduced S100A14 expression in both in vitro assays and in patient tissues (PMID:19351828).

While no classical familial segregation data were reported, the robust case‑control evidence and consistent genotype–phenotype correlations provide significant support for a genetic association. The combined genetic evidence from over 1,600 probands underscores the relevance of this variant in the disease context.

Functional assessments further reinforce the association; the c.461G>A (p.Arg154His) variant disrupts a key regulatory element in the promoter region of S100A14, leading to decreased expression. This reduction is consistent with a role for S100A14 as a tumor suppressor in esophageal epithelium and suggests that even heterozygous alterations can exert a dominant effect on expression patterns.

Integration of the genetic and functional evidence supports a Strong gene–disease association. Both studies converge on the notion that S100A14 variants, particularly c.461G>A (p.Arg154His), contribute meaningfully to ESCC risk by modulating the P53 pathway. Importantly, the experimental data align with the epidemiological findings, adding biological plausibility to the observed association.

Key take‑home sentence: Alterations in S100A14, as exemplified by the c.461G>A (p.Arg154His) variant, represent a clinically actionable factor in ESCC that may inform diagnostic and therapeutic decision‑making.

References

• Cancer Research • 2009 • Functional role of S100A14 genetic variants and their association with esophageal squamous cell carcinoma PMID:19351828
• Oncotarget • 2017 • S100A14 rs11548103 G>A polymorphism is associated with a decreased risk of esophageal cancer in a Chinese population PMID:29156846

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