Of relevance to our study, modifications to this pathway can be induced by high insulin and IGF1, and often occur during early stages of CRC development.39 Third, the calcium-sensing receptor (CaSR) is down-regulated in CRC, indicating that CaSR may act as a potential tumour suppressor in the colorectum,40 providing additional support for a potential causal link between calcium and CRC development. Here, INS is linked to neoplasm.