AGER and type 2 diabetes mellitus: The major RAGE axis-related and underlying molecular mechanisms inducing CRC in patients with type 2 diabetes may include the following: 1) AGE–RAGE interaction promotes the activation of multiple signaling cascades, including the NADPH oxidase, Jak/Stat, and MAPK cascades, resulting in the activation of transcription factors, such as nuclear factor kB (NF-kB), or IFN-stimulated response elements (ISRE), which are involved in proliferation, metastasis, tumor generation [22].