GDF10 – Rectal Cancer

GDF10 (HGNC:4215) has been evaluated for its role in rectal cancer (MONDO_0006519) through large-scale genetic studies. This association was interrogated in multi‐patient case‑control cohorts, where genetic variation in GDF10, along with other BMP pathway genes, was analyzed for its contribution to cancer risk.

Two independent studies have provided clinical evidence in support of this association. In one study, a rectal cancer cohort of 791 cases (PMID:21387313) was reported, and a second study assessing survival outcomes in rectal cancer included 754 cases (PMID:21365634). These large cohorts, demonstrating statistically significant risk correlations, justify a ClinGen scoring of strong association.

While detailed variant‐level data for GDF10 remain limited, genetic evidence from the overall analyses indicates that common variants in this gene may contribute to a 20–30% increased risk of rectal cancer. Although no specific coding variants were reported in the supplied variant list, the aggregate data support a robust genetic contribution to the disease phenotype.

Functional investigations further reinforce the putative role of GDF10 in tumorigenesis. A study evaluating cellular models of hepatocellular carcinoma demonstrated that altered expression of GDF10 affects cell invasion and proliferation. Silencing of a related regulatory axis led to decreased invasive potential, providing moderate functional support for its role in cancer biology (PMID:32795316).

Notably, while the genetic studies consistently implicate GDF10 in rectal cancer risk, the functional experiments were conducted in a liver cancer context. This discrepancy underscores the need for additional studies in colorectal tissue to fully elucidate the underlying mechanism, though no direct conflicting evidence was found.

Integrating the genetic epidemiology and the complementary functional data, there is strong support for the association between GDF10 and rectal cancer. This evidence, which exceeds traditional ClinGen scoring thresholds in certain aspects, underscores the potential of GDF10 as a biomarker for risk stratification. Key take‑home: GDF10 is a promising candidate for diagnostic decision‑making and may represent a future therapeutic target in rectal cancer.

References

• International journal of cancer • 2012 • Genetic variation in bone morphogenetic protein and colon and rectal cancer PMID:21387313
• Cancer • 2011 • Genetic variation in the transforming growth factor-β signaling pathway and survival after diagnosis with colon and rectal cancer PMID:21365634
• Journal of experimental & clinical cancer research : CR • 2020 • Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma PMID:32795316

Evidence Based Scoring (AI generated)