Cytokines such as IL-1β, IL-6, and TNF regulate the expression of DNA methyltransferases DNMT1 and DNMT3B, leading to alterations in gene methylation and expression patterns in pathways implicated in CRC, including those involving NOTCH or p53 signaling.100 Furthermore, NOTCH signaling has been implicated in driving metastasis in KRAS-driven CRC via TGF-β-mediated neutrophil recruitment and in promoting invasion and metastasis in a CMS4 tumor model.61 Inflammation-related RONS and cytokines are parallel mechanisms that mutually reinforce each other. This evidence concerns the gene TGFB1 and neoplasm.