The mechanism underlying the changes of NTSR1 methylation remains unclear, but what is known suggests several possibilities: (1) precursor cells without NTSR1 methylation may selectively survive during the malignant progression, (2) methylated CpG island of NTSR1 in precursor cells may be actively demethylated during the progression from adenoma to carcinoma, and/or (3) the unmethylated NTSR1 allele may be amplified in cancer cells. Here, NTSR1 is linked to adenoma.