2 - Induction of Epigenetic Alterations by Chronic Inflammation and Its Significance on Carcinogenesis
Introduction
Chronic inflammation is deeply involved in development and progression of human cancers, contributing up to 25% of them (Hussain and Harris, 2007). As mechanisms of how chronic inflammation induces irreversible genetic/epigenetic alterations, acceleration of cell proliferation and production of reactive oxygen species (ROS) have been mainly considered. At the same time, as involvement of epigenetic alterations in development and progression of cancers became apparent, induction of epigenetic alterations has joined the mechanisms of how chronic inflammation induces cancers.
In this chapter, we will describe the relationship between inflammation and cancers before the epigenetic era, epigenetic alterations induced by chronic inflammations, and how epigenetic alterations are induced.
Section snippets
Traditional Views on How Inflammation Leads to Cancers
Specific types of inflammation are closely associated with cancer development and progression, and the association had been attributed mainly to induction of cell proliferation and mutations.
Epigenetic Alteration Induced by Inflammation and Its Significance on Carcinogenesis
In addition to mutations, epigenetic alterations are now recognized to be induced by chronic inflammation, and the induction of epigenetic alterations is an important mechanism of how inflammation leads to carcinogenesis.
Mechanisms for Induction of Epigenetic Alterations by Inflammation
Mechanisms for induction of epigenetic alterations by inflammation are still unclear. Inflammation is characterized by disturbance of cytokine signals and induction of cell proliferation, but it is still unclear how these abnormalities lead to induction of aberrant DNA methylation. Although it had been unclear whether there is gene specificity in methylation induction by inflammation, the presence of specificity and its mechanisms are becoming clear.
Conclusions
Chronic inflammation appears to induce aberrant epigenetic alterations, and the induction is likely to be one of the major mechanisms of how chronic inflammation induces cancers. However, the molecular mechanisms underlying induction of aberrant DNA methylation are largely unknown. Research focusing on individual cytokines and chemokines and local balance between DNMTs and protecting factors, such as the presence of Pol II, along with histone modification alterations induced by inflammation,
Acknowledgment
This study was supported by Grants-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan.
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