Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Adv Genet. 2010;71:3-39. doi: 10.1016/B978-0-12-380864-6.00001-8.
Dietary and other environmental factors induce epigenetic alterations which may have important consequences for cancer development. This chapter summarizes current knowledge of the impact of dietary, lifestyle, and environmental determinants of cancer risk and proposes that effects of these exposures might be mediated, at least in part, via epigenetic mechanisms. Evidence is presented to support the hypothesis that all recognized epigenetic marks (including DNA methylation, histone modification, and microRNA (miRNA) expression) are influenced by environmental exposures, including diet, tobacco, alcohol, physical activity, stress, environmental carcinogens, genetic factors, and infectious agents which play important roles in the etiology of cancer. Some of these epigenetic modifications change the expression of tumor suppressor genes and oncogenes and, therefore, may be causal for tumorigenesis. Further work is required to understand the mechanisms through which specific environmental factors produce epigenetic changes and to identify those changes which are likely to be causal in the pathogenesis of cancer and those which are secondary, or bystander, effects. Given the plasticity of epigenetic marks in response to cancer-related exposures, such epigenetic marks are attractive candidates for the development of surrogate endpoints which could be used in dietary or lifestyle intervention studies for cancer prevention. Future research should focus on identifying epigenetic marks which are (i) validated as biomarkers for the cancer under study; (ii) readily measured in easily accessible tissues, for example, blood, buccal cells, or stool; and (iii) altered in response to dietary or lifestyle interventions for which there is convincing evidence for a relationship with cancer risk.
饮食和其他环境因素会引起表观遗传改变，这些改变可能对癌症的发展产生重要影响。本章总结了饮食、生活方式和环境因素对癌症风险的影响的现有知识，并提出这些暴露的影响可能至少部分通过表观遗传机制介导。有证据表明，所有公认的表观遗传标记（包括 DNA 甲基化、组蛋白修饰和 microRNA (miRNA) 表达）都受到环境暴露的影响，包括饮食、烟草、酒精、体育活动、压力、环境致癌物、遗传因素和传染病，这些因素在癌症的病因学中起着重要作用。其中一些表观遗传修饰改变了肿瘤抑制基因和癌基因的表达，因此可能是肿瘤发生的原因。需要进一步的研究来了解特定环境因素产生表观遗传变化的机制，并确定那些可能是癌症发病机制中因果关系的变化，以及那些是次要的或旁观者效应的变化。鉴于表观遗传标记对与癌症相关的暴露具有可塑性，这些表观遗传标记是开发替代终点的有吸引力的候选者，这些替代终点可用于癌症预防的饮食或生活方式干预研究。未来的研究应集中于确定以下表观遗传标记：(i) 已被验证为研究癌症的生物标志物；(ii) 可在容易获得的组织中（例如血液、口腔细胞或粪便）进行测量；以及 (iii) 可因有充分证据表明与癌症风险相关的饮食或生活方式干预而改变。
