In this pathway, IGF-I/IR traits (circulating levels of IGF-I, IGFBP3, insulin, glucose, and HOMA-IR) have two different roles in the relationship between the genetic variants and CRC: mediator (in relation to IGF-I/IR traits–related genetic variants) and influencing factor (in relation to IGF-I/IR signaling pathways–related genetic variants). This evidence concerns the gene IGFBP3 and colorectal carcinoma.