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Recent genome‑wide association studies (GWAS) have consistently implicated GDF7 in the risk for esophageal adenocarcinoma. GDF7, a gene involved in foregut development, has been identified through multiple independent studies as harboring regulatory variants that increase disease susceptibility (PMID:27573776). These studies highlight associations that were initially defined in Barrett's esophagus cohorts, with subsequent analyses demonstrating that the risk alleles also elevate esophageal adenocarcinoma risk. The replicated GWAS signals provide robust statistical evidence across large multi‑patient cohorts.
In one of the key studies, over 10,000 patients were evaluated, and significant signals were observed at the locus near GDF7, particularly for the intronic SNP rs3072 (PMID:25447851). Another independent analysis further confirmed that the Barrett‑associated risk at this locus extends to esophageal adenocarcinoma (PMID:26783083). Although these variants are non‑coding, they likely influence gene regulation, contributing to disease pathogenesis through altered expression profiles.
The genetic evidence is driven by the identification of consistent association signals across three independent studies. Notably, the variant signal near GDF7 (rs3072) has been repeatedly observed; however, no coding change meeting the HGVS criteria (i.e. a c. variant) has been published. As such, no definitive HGVS variant string is available from the supplied evidence, emphasizing a regulatory mechanism rather than a protein‑altering mutation.
Functional evidence, while currently more limited, points to the biological plausibility of GDF7’s role in esophageal tissue development. No direct mechanistic assays or experimental models were provided in the source studies; hence, the experimental support remains to be fully delineated. This gap highlights the need for further functional studies to clarify the pathogenic mechanism of the observed regulatory variants.
The integration of genetic and preliminary functional insights strengthens the overall association between GDF7 and esophageal adenocarcinoma. The repeated replication of GWAS signals across large, diverse cohorts underscores the robustness of the genetic association. Although additional functional data would enhance our understanding, the available evidence is sufficient to support the clinical utility of testing for GDF7 regulatory variation in risk assessment and potential diagnostic applications.
Key take‑home: The strong and replicated genetic evidence for GDF7—with consistent GWAS signals across independent studies—renders it a promising marker for esophageal adenocarcinoma, meriting further functional validation to refine its role in disease pathogenesis.
Gene–Disease AssociationStrongThree independent GWAS studies report significant associations with esophageal adenocarcinoma risk, including analyses in cohorts exceeding 10,000 patients ([PMID:25447851]). Genetic EvidenceStrongMultiple studies consistently identified intronic regulatory signals near GDF7 (notably rs3072) that are reproducibly associated with increased disease risk. Functional EvidenceLimitedNo direct functional assays were provided; the evidence is currently restricted to genetic associations without mechanistic validation. |