Johnson Ian T, Belshaw Nigel J
Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
Food Chem Toxicol. 2008 Apr;46(4):1346-59. doi: 10.1016/j.fct.2007.09.101. Epub 2007 Sep 26.
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.
哺乳动物消化道的上皮表面具有细胞增殖和DNA合成速率极高的特点，在人类中，这些上皮表面极易患癌。体细胞突变作为消化道致癌作用驱动因素的作用已得到充分证实，但表观遗传机制导致的基因沉默的重要性也日益受到认可。CpG岛的甲基化是表观遗传密码的重要组成部分，在发育和正常细胞分化过程中调节基因表达，并且已知许多基因在食管、胃和结肠直肠癌的肿瘤发生过程中会发生异常甲基化。DNA甲基化的异常模式是由慢性炎症等病理过程导致的，并且是对各种饮食因素的反应，这些因素包括甲基供体供应失衡，尤其是叶酸，以及接触DNA甲基转移酶抑制剂，其中包括多酚类物质以及可能来自植物性食物的异硫氰酸盐。然而，这些环境相互作用在人类健康和疾病中的重要性仍有待确定。最近通过强制补充谷物食品来改变人群叶酸摄入量的举措，凸显了了解人类表观基因组对饮食和其他环境影响易感性的重要性。
