Figure 1: Bowel microenvironment influences CRC molecular features and progression. The CIMP-high, MSI-high, and BRAF mutations frequencies gradually increase from the rectum to ascending colon. Caecal cancers seem to represent a distinct subtype characterized by a higher frequency of KRAS mutations, a MSS, and CIMP-L phenotype. In the bowel microenvironment, changes in the balance between (1) microbiome, food debris, and bacterial fermentation products and (2) interactions with host cells (epithelial and immune cells) might predispose colon epithelial cells to certain molecular insults and differentially influence tumour development according to molecular features in preneoplastic cells. CpG island methylator phenotype: CIMP; microsatellite instability: MSI; CIMP-low: CIMP-L.