WASL – Gastric Cancer

This summary reviews the association between WASL (HGNC:12735) and gastric cancer (MONDO_0001056) as reported in a multi‐patient genetic association study. In a large-scale assessment using a genome-wide framework, germline variants in the EGFR signaling pathway were analyzed in 1758 gastric cancer cases (PMID:23874846) and 2111 controls. The gene-level analysis identified WASL among 10 genes with a statistically significant association to gastric cancer risk.

The genetic evidence is derived from a case–control study rather than familial segregation analyses. Although the study encompassed a considerable sample size, no additional independent familial co-segregation data or replication studies are available to bolster a definitive genetic link. Thus, clinical interpretation must be approached with caution.

A representative variant observed in WASL from other studies, namely c.1139C>T (p.Pro380Leu), is provided as an example of the variant spectrum encountered in WASL. This variant meets the full HGVS criteria and serves as a reference point, despite its original association with a different phenotype (Parkinson’s disease) rather than gastric cancer. Its inclusion demonstrates the type of coding alterations present in WASL and underscores the need for further disease-specific variant characterization.

Functionally, WASL is known to regulate actin dynamics and may influence cellular processes through modulation of the EGFR and Wnt signaling pathways. While functional assessment studies in other clinical contexts (e.g., ulcer disease, alopecia) underscore its role in relevant cell signaling and cytoskeletal reorganization, no direct functional studies have established a mechanism linking WASL perturbations to gastric carcinogenesis. This lack of direct experimental data limits the experimental support for the association with gastric cancer.

In summary, the current evidence for the association between WASL and gastric cancer is based on a statistically significant gene-level finding in a single multi-patient study, with no supportive segregation or direct functional data in the context of gastric cancer. The integration of these findings highlights that while WASL may contribute to the disease risk via its involvement in critical signaling pathways, further replication and mechanistic studies are needed to firmly establish its clinical utility.

Key take‑home sentence: Although WASL shows a significant association with gastric cancer risk in large cohort analyses, additional functional and segregation evidence is required to confidently implement these findings in clinical decision‑making and commercial diagnostic settings.

References

• PloS one • 2013 • Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population PMID:23874846

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