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Gastroenterology. 2012 Sep;143(3):550-563. doi: 10.1053/j.gastro.2012.07.009. Epub 2012 Jul 13.

Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation.

Author information

1
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: chiba@kuhp.kyoto-u.ac.jp.
2
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
3
Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.

Abstract

Chronic inflammation, regardless of infectious agents, plays important roles in the development of various cancers, particularly in digestive organs, including Helicobacter pylori-associated gastric cancer, hepatitis C virus-positive hepatocellular carcinoma, and colitis-associated colon cancers. Cancer development is characterized by stepwise accumulation of genetic and epigenetic alterations of various proto-oncogenes and tumor-suppressor genes. During chronic inflammation, infectious agents such as H pylori and hepatitis C virus as well as intrinsic mediators of inflammatory responses, including proinflammatory cytokines and reactive oxygen and nitrogen species, can induce genetic and epigenetic changes, including point mutations, deletions, duplications, recombinations, and methylation of various tumor-related genes through various mechanisms. Furthermore, inflammation also modulates the expressions of microRNAs that influence the production of several tumor-related messenger RNAs or proteins. These molecular events induced by chronic inflammation work in concert to alter important pathways involved in normal cellular function, and hence accelerate inflammation-associated cancer development. Among these, recent studies highlighted an important role of activation-induced cytidine deaminase, a nucleotide-editing enzyme essential for somatic hypermutation and class-switch recombination of the immunoglobulin gene, as a genomic modulator in inflammation-associated cancer development.

PMID:
22796521
DOI:
10.1053/j.gastro.2012.07.009
[Indexed for MEDLINE]
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