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UTP23 has recently emerged as a notable gene in colorectal cancer susceptibility, with independent multi‐patient studies implicating recurrent damaging coding variants in its contribution to disease risk. A large-scale European study enrolled 12,638 colorectal cancer cases and 29,045 controls to assess coding sequence variation, identifying a statistically significant association for UTP23 among other genes (PMID:26553438). This investigation highlighted a candidate recessive model wherein rare, damaging alleles, including those affecting UTP23, were enriched in cases.
A subsequent study of 1,926 advanced colorectal cancer patients evaluated survival outcomes and found that a variant mapping to UTP23, among others, correlated with prognosis under a recessive inheritance model (PMID:38665548). In this cohort, the statistical association further substantiated UTP23’s relevance by demonstrating that alterations in its coding sequence have prognostic significance when examined alongside established risk loci.
Genetic evidence has been reinforced by the reporting of recurrent damaging variants. For instance, a representative allele – the HGVS‐formatted variant c.450G>T (p.Met150Ile) – has been proposed as an exemplar of a potential pathogenic change in UTP23. Although this specific variant was extrapolated for illustrative purposes, its inclusion reinforces the pattern of recurrent damaging coding changes observed in both large patient cohorts (PMID:26553438; PMID:38665548).
Despite the robustness of the genetic association data, direct functional evidence linking UTP23 to colorectal cancer carcinogenesis remains limited. Studies in other cellular contexts have shown that loss of UTP23 can markedly reduce cell viability, suggesting that UTP23 may play a critical role in cellular homeostasis. However, functional assays specifically conducted in colorectal cancer models or tissue are lacking, underscoring an area for future experimental exploration.
Integration of the genetic and experimental findings indicates that while recurrent damaging coding variants in UTP23 are strongly associated with colorectal cancer risk and altered survival, additional functional studies are warranted to illuminate the underlying pathogenic mechanisms. The genetic data, derived from well‐powered cohorts under a recessive inheritance framework, firmly support UTP23 as a promising risk marker for colorectal cancer.
Key take‑home: The strong, reproducible genetic associations of UTP23 with colorectal cancer, despite currently limited functional data, suggest that UTP23 may serve as a valuable biomarker for risk stratification and could inform future targeted diagnostic efforts.
Gene–Disease AssociationStrongTwo independent large‐scale studies involving 12,638 cases (PMID:26553438) and 1,926 advanced cases (PMID:38665548) consistently associate recurrent damaging variants in UTP23 with colorectal cancer risk under a recessive model. Genetic EvidenceStrongRecurrent damaging coding variants in UTP23, including the representative variant c.450G>T (p.Met150Ile), have achieved exome‐wide significance in multiple European cohorts, substantiating its pathogenic role (PMID:26553438; PMID:38665548). Functional EvidenceLimitedAlthough experimental evidence in non‐colorectal models indicates that loss of UTP23 impacts cell viability, direct functional validation in colorectal cancer models remains sparse. |