SMAD3 and colorectal carcinoma: Abnormal hypomethylation of some genes, such as mothers against decapentaplegic homolog 3 (SMAD3), long interspersed nucleotide element-1 (LINE-1) and GDNF family receptor alpha 1 (GFRA1) genes, have been shown to be associated with the poor prognosis of CRC [31,32,33].