Association Of Extensive Delayed Overmethylation Influenced By Advanced Atrophy With Risk For Gastric Cancer

13 Background: Helicobacter pylori (HP) infection facilitates overmethylation of CpG-island genes, which can be delayed by advanced mucosal atrophy. Delayed overmethylation results in unstable cell phenotypes responsible for gastric cancer. To delineate cancer risk period, the overmethylation period from HP infection to severe atrophy was traced in the gastric cancer and dysplasia. Methods: A pair of normal-appearing mucosal specimens was obtained from the antrum and body of 110 HP-positive and 95 HP-negative controls, 99 cancer patients, and 118 dysplasia patients. Gastric mucosal atrophy was assessed using the endoscopic atrophic border score. Eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, TRAPPC2L) and LTR retroelements (MMP2, CDKN2A, RUNX2, RUNX3) and the TFF3 gene lacking CpG island were chosen. The methylation-variable sites in gene-control regions were analyzed using radioisotope-labeling methylation-specific PCR. Results: The antrum-specific TFF3 gene on the antrum tended to be overm...