ArticleScience advances2026
Systematic analysis of functional genetic and epigenetic variants in colorectal cancer.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the functional impact of noncoding variants on enhancer activity remains largely unexplored. In this study, we adapted and applied two high-throughput techniques, SNP-STARR-seq and Methyl-STARR-seq, to systematically evaluate the influence of 30,790 noncoding SNPs and more than 134,000 CpG sites on enhancer activity in primary and metastatic CRC cells. We identified 922 SNPs and 487 CpG-containing elements modulating enhancer activity in primary cells and found 3136 SNPs and 3008 methylation-sensitive elements with metastasis-specific regulatory effects. Multi-omics integration linked these variants to target genes, and CRISPR editing validated their roles in driving tumorigenic and metastatic phenotypes. Furthermore, we identified two CRC-specific hypermethylated loci, cg08640619 and cg25982657, as exceptional tissue-based early detection biomarkers (AUC > 0.96). Mechanistically, hypermethylation at cg08640619 disrupts RUNX2 binding, leading to inhibition of
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