The signal-transduction pathways dysregulated by DNA methylation changes in both obesity and CRC include: 1) extracellular matrix components, i.e., O-glycan processing, protein glycosylation, and extracellular matrix scaffold; 2) KRAS and TGF-β signaling; and 3) lipid and glucose metabolism (Table 2 and Fig. 4). Here, TGFB1 is linked to obesity due to melanocortin 4 receptor deficiency.