Article

Environment, diet and CpG island methylation: Epigenetic signals in gastrointestinal neoplasia

Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK. <>
Food and Chemical Toxicology (Impact Factor: 2.9). 05/2008; 46(4):1346-59. DOI: 10.1016/j.fct.2007.09.101
Source: PubMed

ABSTRACT

The epithelial surfaces of the mammalian alimentary tract are characterised by very high rates of cell proliferation and DNA synthesis, and in humans they are highly susceptible to cancer. The role of somatic mutations as drivers of carcinogenesis in the alimentary tract is well established, but the importance of gene silencing by epigenetic mechanisms is increasingly recognised. Methylation of CpG islands is an important component of the epigenetic code that regulates gene expression during development and normal cellular differentiation, and a number of genes are well known to become abnormally methylated during the development of tumours of the oesophagus, stomach and colorectum. Aberrant patterns of DNA methylation develop as a result of pathological processes such as chronic inflammation, and in response to various dietary factors, including imbalances in the supply of methyl donors, particularly folates, and exposure to DNA methyltransferase inhibitors, which include polyphenols and possibly isothiocyanates from plant foods. However the importance of these environmental interactions in human health and disease remains to be established. Recent moves to modify the exposure of human populations to folate, by mandatory supplementation of cereal foods, emphasise the importance of understanding the susceptibility of the human epigenome to dietary and other environmental effects.

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    • "DNA methylation, which occurs primarily in the C5 position of the cytosine ring in 5=-to 3=-oriented CG dinucleotides (CpG), affects gene expression in many biological processes such as differentiation, genomic imprinting , and DNA mutation and repair [10] [11]. DNA hypermethylation , usually occurring at promoter CpG islands, is a major epigenetic mechanism for silencing the expression of genes [12] and is tightly regulated by three different DNA methylases involved in de novo and maintenance methylation during replication [9] [13]. Other DNA methyl group transfer-related enzymes are demethylases, which act by demethylating DNA during differentiation [14]. "
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