Germline mutations of POLE and POLD1 ED in CRC are less frequent (0.3–0.7%), but they are involved in the development of multiple colorectal adenomas and carcinomas, causing the polymerase proofreading-associated polyposis (PPAP), which can be associated also with increased risk of non-colonic cancers [52]. Here, POLE is linked to colorectal carcinoma.