How chronic inflammation fuels carcinogenesis as an environmental epimutagen

Abstract

Abstract Chronic inflammation, induced by environmental and intrinsic factors, frequently leads to carcinogenesis. In inflammation-associated cancers, such as gastric, colon, and cervical cancers, an important role of epigenetic alterations has been implicated. Such epigenetic alterations include aberrant DNA methylation and histone modifications, some of which can permanently alter cellular characteristics and predispose cells to malignant transformation. Even in normal-appearing tissues, high levels of aberrant DNA methylation can be present, with these levels correlating to future cancer risk. The mechanisms of how chronic inflammation induces aberrant DNA methylation involve the repression of DNA methylation erasers, TET enzymes, and the increased activity of DNMTs. Aberrant DNA methylation in normal tissues can serve as a biomarker for cancer risk in the stomach and uterus. Beyond chronic inflammation, factors such as folate, vitamin B12, and vitamin C deficiency can affect DNA methylation through metabolic pathways. Additionally, environmental chemicals, such as arsenic and NNK, and microbial metabolites, have been implicated in inducing epigenetic alterations. Further research is warranted on epigenetic alterations due to environmental factors, and the factors themselves, namely epimutagens.

Keywords

• Chronic inflammation
• Carcinogenicity
• DNA methylation
• Epimutagen