Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dig Dis. 2011;29(2):130-5. doi: 10.1159/000323874. Epub 2011 Jul 5.
Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA. The predominant epigenetic mechanisms are DNA methylation, modifications to chromatin, loss of imprinting and non-coding RNA. Epigenetic regulation of gene expression appears to have long-term effects and wide-ranging effects on health. Diet and environmental exposures may potentially alter the level and scope of epigenetic regulation, thus interesting developments in the study of epigenetics might explain correlations that researchers have found between lifestyle and risk of disease. Aberrant epigenetic patterns have been linked to a number of digestive diseases including Barrett's esophagus, cirrhosis, inflammatory bowel disease, and numerous gastrointestinal malignancies. In fact, many exciting discoveries about epigenetics in general have been made by studying diseases of the gastrointestinal tract and hepatobiliary tree. Epigenetic modifications of DNA in cancer and precancerous lesions offer hope and the promise of novel biomarkers for early cancer detection, prediction, prognosis, and response to treatment. Furthermore, reversal of epigenetic changes represents a potential target of novel therapeutic strategies and medication design. In the future, it is anticipated that innovative diagnostic tests, treatment regimens, and even lifestyle modifications will be based on epigenetic mechanisms and be incorporated into the practice of medicine.
表观遗传学被定义为基因表达的可遗传变化,与突变不同,这些变化不能归因于 DNA 序列的改变。主要的表观遗传机制有 DNA 甲基化、染色质修饰、印记丢失和非编码 RNA。基因表达的表观遗传调控似乎具有长期效应,并对健康产生广泛影响。饮食和环境暴露可能会改变表观遗传调控的水平和范围,因此,在表观遗传学研究中有趣的进展可能会解释研究人员在生活方式与疾病风险之间发现的相关性。异常的表观遗传模式与许多消化系统疾病有关,包括巴雷特食管、肝硬化、炎症性肠病和许多胃肠道恶性肿瘤。事实上,通过研究胃肠道和肝胆树的疾病,人们已经对表观遗传学的许多令人兴奋的发现有了了解。在癌症和癌前病变中,DNA 的表观遗传修饰为早期癌症检测、预测、预后以及对治疗的反应提供了希望和新的生物标志物的承诺。此外,表观遗传变化的逆转代表了新的治疗策略和药物设计的潜在目标。在未来,预计创新的诊断测试、治疗方案甚至生活方式的改变都将基于表观遗传机制,并纳入医学实践。