Colorectal cancer (CRC) remains a major global health concern, especially given its increasing incidence among younger individuals. While genome-wide association studies (GWAS) have identified numerous CRC-associated polymorphisms, their spatial distribution and functional implications are not fully understood. This study examined the locations of 1,346 CRC-linked polymorphisms across chromosomal bands. The results revealed significant nonrandom clustering across thirteen chromosomal bands: 1q41, 6p21, 8q24, 9q34, 10p14, 10q25, 11q12, 12p13, 15q13, 18q21, 19q13, 20p12, and 20q13. Functional enrichment analysis of genes within these bands revealed several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Reciprocal chromosomal enrichment confirmed that many of these terms and pathways were not randomly localized within the same bands, highlighting their potential biological significance. Survival analysis using TCGA data identified three KEGG pathways and 33 GO terms mapped to nine of the thirteen bands that were significantly associated with poor prognosis. Notably, the 8q24 and 20q13 regions were enriched for differentially expressed genes and survival-associated terms yet showed no significant enrichment for genes with high somatic mutation rates. These results imply that 8q24 and 20q13 act as regulatory hotspots rather than mutation-driven regions. Overall, this integrative approach identified functionally and clinically relevant genomic regions that may contribute to inherited CRC risk and progression, providing valuable targets for the development of diagnostic and prognostic biomarkers. |