Allele-Specific MicroRNA-Binding Variants at Colorectal Cancer Risk Loci in a Hispanic/Latino Population: An Integrative GWAS, All of Us, and Epigenomic Analysis

The study examined genetic variants associated with colorectal cancer in the Hispanic population using GWAS analysis and data from the All of Us Research Program (n = 453). Researchers identified 19 variants in 3' untranslated regions of genes that alter microRNA binding across nine genes. Three major genes - DCBLD2, GREM1, and SMC1B - met all prioritization criteria and were selected as strong candidates. In each case, the risk allele disrupts a strong microRNA-binding site, leading to increased gene expression in tumors. The results suggest that these variants promote gene overexpression through loss of microRNA-mediated repression rather than changes in promoter methylation. The study emphasizes that the Hispanic population has been underrepresented in genomic research.