Gastric cancer and related epigenetic alterations

Abstract

Gastric cancer, a malignant and highly proliferative condition, has significantly affected a large population around the globe and is known to be caused by various factors including genetic, epigenetic, and environmental influences. Though the global trend of these cancers is declining, an increase in its frequency is still a threat because of changing lifestyles and dietary habits. However, genetic and epigenetic alterations related to gastric cancers also have an equivalent contribution towards carcinogenic development. DNA methylation is one of the major forms of epigenetic modification which plays a significant role in gastric carcinogenesis. Methylation leads to inactivation of some of the most important genes like DNA repair genes, cell cycle regulators, apoptotic genes, transcriptional regulators, and signalling pathway regulators; which subsequently cause uncontrolled proliferation of cells. Mutations in these genes can be used as suitable prognostic markers for early diagnosis of the disease, since late diagnosis of gastric cancers has a huge negative impact on overall patient survival. In this review, we focus on the important epigenetic mutations that contribute to the development of gastric cancer and the molecular pathogenesis underlying each of them. Methylation, acetylation, and histone modifications play an integral role in the onset of genomic instability, one of the many contributory factors to gastric cancer. This article also covers the constraints of incomplete knowledge of epigenetic factors influencing gastric cancer, thus throwing light on our understanding of the disease.

Association of peripheral blood leukocyte KIBRA methylation with gastric cancer risk: a case–control study

“…Several epidemiological studies have demonstrated that dietary factors and DNA methylation could independently and significantly influence the progression of GC , while dietary factors play an important role not only in tumorigenesis but also in inducing DNA methylation , hence their interactions and combinations were explored in this study subsequently. Results showed that significant combinations were obviously observed between the dietary factors and KIBRA methylation on the GC risk, but no interactions were found.…”

Major Hereditary Gastrointestinal Cancer Syndromes: a Narrative Review

“…26 No 2: 157-163 [24]. The pathogenesis of gastric cancer is the result of the interaction between environmental and genetic factors [24,25].…”

“…Activation of K-ras and β-catenin oncogenes, mutation of the p53 tumor suppressor gene and MSI have been associated with both histological types. Amplification of C-erb and C-met genes has been found in about 10% of both histological types [24,25]. Somatic mutation of CDH1 has been associated with diffuse gastric cancer specifically [24,25].…”

“…In addition to these known genetic mutations, epigenetics has been found to have a significant clinical impact on the development of gastric neoplasia. The major epigenetic process that plays a role in the pathogenesis of gastric cancer is DNA methylation [24,25]. DNA methyltransferases (DNMTs) catalyze the modification of cytosine in the CpG islands resulting in inactivation of the gene and repressing transcription.…”

“…Histones are highly alkaline, rich in lysine and arginine amino acids that are positively charged and interact with the negatively charged DNA to package it into nucleosomes. In gastric cancer, histone 3 acetylation and methylation of lysine 9 residues on histone 3 have been associated with the silencing of the tumor suppressor gene and subsequent tumorigenesis [24,25].…”