IGF1 and obesity due to melanocortin 4 receptor deficiency: Plausible biological mechanisms include subclinical low-grade inflammation, oxidative stress, insulin resistance and abnormalities of the insulin-like growth factor 1 system, and signaling and sex hormones biosynthesis and pathways.16 Recent evidence also suggests a possible role of obesity-associated change of gut microbiota in the development of CRC.4,17 Gene-environment interaction studies might help to unravel the mechanisms through which obesity is associated with carcinogenesis.