Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of<i>H. pylori</i>eradication on DNA methylation

Abstract

Objective It remains unknown whether individuals with a family history (FH) of gastric cancer (GC) are associated with aberrant DNA methylation. The aim of this study was to investigate the association between aberrant DNA methylation and FH of GC. Design Using quantitative MethyLight assay,MOS,miR124a-3,NKX6-1,EMX1,CDH1, andTWIST1methylation levels in the noncancerous gastric mucosa was compared between subjects with and without FH based on GC andHelicobacter pylori(Hp) infection. Changes in the methylation levels were evaluated over time after Hp eradication. Results In Hp-positive GC patients,MOS(P < 0.001),CDH1(P < 0.001), andTWIST1(P = 0.004) methylation were decreased in subjects with FH (n = 64) than in those without FH (n = 58). In Hp-positive controls,MOSmethylation was lower in subjects with FH (n = 73) than in those without FH (n = 50) (P = 0.042), whilemiR124a-3(P = 0.006),NKX6-1(P < 0.001), andCDH1(P < 0.001) methylation were higher in subjects with FH.CDH1methylation constantly decreased from 2 years in GC patients and 3-4 years in controls after Hp eradication (allP < 0.001). A persistent decrease in methylation over time was not observed in other genes after eradication. Conclusion The methylation ofMOSandCDH1provided an association between aberrant DNA methylation and gastric carcinogenesis in FH of GC, a useful marker for GC risk in individuals with FH. Furthermore,CDH1methylation decreased after Hp eradication.