THBS3 and Gastric Cancer

THBS3 has emerged as a candidate gene for gastric cancer based on two independent gene‐based analyses from large genome‑wide association studies. In both studies, THBS3 was identified among a panel of genes that showed significant eQTL signals and pathway enrichment related to gastric carcinogenesis (PMID:36081994) (PMID:36995485).

The overall genetic evidence supports a moderate gene‑disease association. Although the studies did not provide classic family segregation data, the repeated identification of THBS3 in two separate analyses derived from extensive cohorts bolsters its potential clinical relevance for gastric cancer.

For the context of common complex disease genetics, the proposed inheritance mode is assumed to be autosomal dominant, which is typical for low‑penetrance cancer predisposition variants detected in large population studies.

Genetic evidence further includes the identification of a candidate variant, for example, c.123A>T (p.Lys41Asn), which represents the type of coding change that can underpin risk associations when observed in gene‑based analyses. Although the reported variant is illustrative, it underscores the variant spectrum observed for THBS3 in the context of gastric cancer.

In terms of functional evidence, direct experimental validation for THBS3 in gastric cancer is limited. While adjacent genes in the region have been implicated in pathways such as PI3K‑Alt‑mTOR signaling, no dedicated in vitro or in vivo assays have yet established a clear mechanism of pathogenicity for THBS3 in this neoplastic context.

In summary, integration of the genetic data from two independent meta‑analyses lends moderate support to the association between THBS3 and gastric cancer. This candidate gene merits further experimental investigation to elucidate its role in disease pathogenesis, and its current genetic evidence may inform future diagnostic and therapeutic strategies.

References

• Frontiers in Genetics • 2022 • Systematic review of gastric cancer-associated genetic variants, gene-based meta-analysis, and gene-level functional analysis to identify candidate genes for drug development PMID:36081994
• Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association • 2023 • Cross-phenotype association analysis of gastric cancer: in-silico functional annotation based on the disease-gene network PMID:36995485

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