In a study conducted in 2002, the H19 differentially methylated region (DMR) as well as a DMR upstream of exon 3 of IGF2 were shown to be hypo-methylated in both CRC tissues and normal mucosa [142], whereas a 2012 study showed that hypo-methylation of the sixth CTCF-binding site in the DMR of IGF2/H19 is related to loss of imprinting (LOI), indicating that the LOI of IGF2 plays an important role in CRC [143]. The gene discussed is CTCF; the disease is colorectal carcinoma.