IGF1 and colorectal carcinoma: More importantly, our two-step MR analysis revealed a previously unrecognized dual-pathway mechanism underlying this association, wherein TL influences CRC risk through two opposing biological processes: a procarcinogenic growth signaling pathway mediated by IGF1 (4.20% mediation) and a protective protein metabolism pathway mediated by total protein and nonalbumin protein levels (collectively, 19.67% mediation).