Novel findings of this study include: the genetically predicted expressions of FOXA1, PSMC5 and CD33 modified the association of BMI on CRC risk for men; KIAA0753 and SCN1B modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes. Here, PTPN2 is linked to colorectal carcinoma.