Epigenetic impact of infection on carcinogenesis: mechanisms and applications

Abstract

Viral and bacterial infections are involved in the development of human cancers, such as liver, nasopharyngeal, cervical, head and neck, and gastric cancers. Aberrant DNA methylation is frequently present in these cancers, and some of the aberrantly methylated genes are causally involved in cancer development and progression. Notably, aberrant DNA methylation can be present even in non-cancerous or precancerous tissues, and its levels correlate with the risk of cancer development, producing a so-called ‘epigenetic field for cancerization’. Mechanistically, most viral or bacterial infections induce DNA methylation indirectly via chronic inflammation, but recent studies have indicated that some viruses have direct effects on the epigenetic machinery of host cells. From a translational viewpoint, a recent multicenter prospective cohort study demonstrated that assessment of the extent of alterations in DNA methylation in non-cancerous tissues can be used to predict cancer risk. Furthermore, suppression of aberrant DNA methylation was shown to be a useful strategy for cancer prevention in an animal model. Here, we review the involvement of aberrant DNA methylation in various types of infection-associated cancers, along with individual induction mechanisms, and we discuss the application of these findings for cancer prevention, diagnosis, and therapy.

Roadmap for investigating epigenome deregulation and environmental origins of cancer

“…For example, the maternal microbiome and the postnatal gut microbiome seem to play a role in modulating intestinal mucosal epigenetic patterning and consequent susceptibility to inflammatory bowel disease (IBD) and young‐onset colorectal cancer . Another example is the epigenetic field cancerization observed in gastric cancer, where chronic inflammation induced by Helicobacter pylori is responsible for aberrant DNA methylation . In addition, oncogenic viruses such as Hepatitis B virus and Epstein–Barr virus are known to hijack the host epigenetic machinery to promote its replication and to cloak itself from the host surveillance system, but potentially leaving a recognizable epigenetic signature .…”

Viral driven epigenetic events alter the expression of cancer-related genes in Epstein-Barr-virus naturally infected Burkitt lymphoma cell lines

“…A profound epigenetic remodeling was also shown in EBV-driven epithelial cancers, such as Gastric Cancer (GC) 18 .…”

The Origins of Gastric Cancer From Gastric Stem Cells: Lessons From Mouse Models

“…Furthermore, more than 10% of gastric cancer cases have very few gene mutations, suggesting that genetic events may not be required for cancer initiation and progression 33, 34, 37. It is possible that in many tumors, epigenetic changes induced by chronic Helicobacter infection39, 40 or other factors 41 may play more important roles in triggering cancer initiation. There is strong evidence from analysis of human resection specimens that these mutations are established within stem cells in the gastric glands, and that clonal alterations can spread by means of gland fission 5, 6, 7, 8…”