SMAD4 and colorectal carcinoma: Although up to 35% of CRC susceptibility is considered to be explained by heritability and around 15% of CRC patients have a family history of CRC, less than 5% of all cases are due to highly penetrant germline variants in established predisposition genes, such as APC, mismatch repair genes (MLH1, MSH2, MSH6, PMS2), EPCAM, SMAD4/BMPR1A, and MUTYH, resulting in well-characterized clinical features of known Mendelian CRC syndromes [3,4,5].