SMAD4 and carcinoma: A pioneering model for colorectal tumorigenesis was published in 1990 by Fearon and Vogelstein, in which it was proposed that sequential accumulation of mutations in oncogenes and tumor suppressor genes, such as APC, SMAD4, KRAS, BRAF, and TP53, promote progression from normal colonic epithelium to adenoma, and finally, carcinoma [10].