Gastric cancer (GC) or human gastric adenocarcinoma is one of the most commonplace type of serious cancers and also the most common cause of cancer-related mortality in the world. Relatively, many studies have acknowledged that GC is a multi-factorial pathological situation that environmental factors, particularly dietary ones and H.pylori infection are considered to have a strong key role in the etiology of GC. Inappropriate dietary habits are the first cause as they affect main molecular functions related with the onset of the GC tumorigenesis and carcinogenesis. Correspondingly, cancer investigation has impressively zoomed on the different genetic markers and also molecular mechanisms pathways responsible for the progression of the GC. Various molecular signaling pathways such as WNT, NOTCH, SHH, MYC have different functions and analyzing their role in the GC is of great importance particularly for the treatment modalities. Proportionately, fluctuations of epigenetic alterations including DNA methylation, histone modification, histone acetylation and also histone phosphorylation’s are involved in all cancers specially the GC. Conspicuously, novel developments in cancer epigenetic have indicated immense reprogramming of every structure of the epigenetic mechanism in cancer, comprising microRNAs, nucleosome positioning, DNA methylation, noncoding RNAs, and histone modifications. In this account, aberrant DNA methylation mechanism in the promoter regions of certain genes, which leads to silencing of some particular genes such as tumor suppressor and other cancer-related genes in carcinogenesis, is the most important epigenetic hallmark in human GC especially as a target for detection and diagnosis in cancer treatment.

Here, we review the importance of epigenetic fluctuations alongside with their molecular signaling mechanism in the GC.