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The current evidence linking EIF4EBP3 to colorectal cancer is derived from large, multi‐patient association studies and a functional assessment that together provide a preliminary but limited level of clinical validity. Two independent studies (PMID:21088106, PMID:28061442) evaluated tagSNPs across several genes including EIF4EBP3 in cohorts of up to 1555 colon cancer and 754 rectal cancer cases. These studies identified statistically significant associations with odds ratios ranging from 1.21 to 1.52 for single SNP analyses, with combined high‐risk genotype effects reaching up to 3.32. However, the lack of discrete rare coding variants, absence of multi‐family segregation data, and limited replication of EIF4EBP3‐specific alleles confine the gene–disease association to a limited validity range.
Supporting the genetic data, a functional study (PMID:14557257) revealed that EIF4EBP3 forms a gene fusion transcript with MASK that results in an alternative reading frame of the eIF4E binding region. This finding, which implicates altered translational control via the Ras/MAPK pathway, offers moderate experimental corroboration for a pathogenic mechanism relevant to colorectal tumorigenesis. Nonetheless, the experimental evidence does not directly link the fusion event to colorectal cancer, and further functional and segregation studies are necessary.
Key take‑home sentence: While EIF4EBP3 appears to contribute a modest risk for colorectal cancer based on current association and functional studies, additional robust evidence is needed before it can be fully integrated into clinical diagnostic decision‑making.
Gene–Disease AssociationLimitedStatistically significant tagSNP associations in large colorectal cancer cohorts (PMID:21088106, PMID:28061442) support a potential link to disease; however, the absence of discrete pathogenic variants and robust segregation data imparts a limited clinical validity. Genetic EvidenceLimitedAssociation studies indicate modest risk contributions with combined high‑risk genotype odds ratios up to 3.32; no well‐defined rare or coding variants have been disclosed for EIF4EBP3. Functional EvidenceModerateA gene fusion study (PMID:14557257) demonstrates alternative splicing and reading frame usage involving EIF4EBP3, suggesting a mechanism that may perturb translational regulation via the Ras/MAPK pathway. |