Our results reflect the recently proposed ‘epigenetic priming’ model, whereby epigenetic changes induced by chronic exposure to cigarette smoke were shown to sensitise cells to an oncogenic KRAS mutation by promoting EMT in lung cancer, or the epigenomic alterations driven by obesity were detectable in precancerous colonic epithelium [7, 67]. Here, KRAS is linked to obesity due to melanocortin 4 receptor deficiency.