INSR and diabetes mellitus: Diabetes mellitus (DM), which shares similar risk factors with CRC, has been regarded as an independent CRC-related factor.[5,6] The underlying mechanisms involved in DM-related cancer are correlated with long-term hyperglycemia and hyperinsulinemia, and the former could activate IR and IGF-IR through activating the c-MYC-, PI3K-, MAPK-, or mTOR-pathway to impact cell survival and proliferation.[7–9] Many observational studies have shown the positive relationship between DM and the risk of CRC.