INSR and colorectal carcinoma: Because IGF-I/IR traits are not mediators of the association between SNPs in IGF-I/IR signaling-pathway genes (IRS1 and AKT1/2, in this study) and CRC, instead of estimating the mediation effect of the traits, we estimated a proportion explained by the traits as an influencing factor of the SNP–cancer relationship (Fig 2).