Revista de carcinogénesis y mutagénesis

Abstracto

Helicobacter pylori Infection, DNA Methylation, and Gastric Carcinogenesis

Ya-Bin Qi, Ruo-Bing Hu, Song-Ze Ding*, Muhammad Noman Khan, Lei Lei, Pei-Ru Wei, Bai-Ling Jia

Helicobacter pylori (H. pylori), the major cause of chronic gastritis, peptic ulcers and gastric cancer, infects about 50% of the world population. Although various host and bacterial factors have been suggested, the detailed pathogenic mechanisms remain to be defined. Increasing evidences have demonstrated that epigenetic dysregulation, such as DNA methylation, plays a critical role in gastric carcinogenesis, and is currently under intensive investigation. H. pylori infection result in aberrant DNA methylation in a number of gene promoters in gastric mucosa, eradication of H. pylori can reverse some hypermethylated genes, but had no effect on others. In some methylated genes, the methylation levels persist even after H. pylori eradication, and the fact suggests that DNA methylation accumulation is associated with molecular irreversibleness and gastric diseases progression. DNA methylome and gastric cancer risk analysis indicate that certain gene promoter methylation may serve as potential biomarkers for gastric cancer predication. In addition, H. pylori cagA and vacA s1m1 genotype are independent variables that is associated with higher methylation level. The levels of methylation can be influenced by the degree and length of infection exposure, and certain host gene polymorphisms are also associated with gene methylation in H. pylori-infected subjects. Continued investigation in these areas will be critical to provide insights into the molecular mechanisms of H. pylori induced gastric diseases and develop strategies for disease prevention and intervention. We review recent progress and discuss future research directions in this important area.