TP53 and cancer: These genes play critical roles in various cellular processes necessary for cancer progression, including DNA repair, cell cycle regulation, cell adhesion, apoptosis, and angiogenesis [41], which include APC, p53, p27, MSI, LOH 18q, deletion 5q allele, and DNA hypermethylation [38]. However, the combined effects of accumulated hypermethylation and hypomethylation on CRC development and outcome remain understudied [42,43].