International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, Lyon, 69008, France.
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Int J Cancer. 2018 Mar 1;142(5):874-882. doi: 10.1002/ijc.31014. Epub 2017 Sep 13.
The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific ("fingerprints") that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed and advances in epigenomics that may help in understanding the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed and how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment.
个体的（表观）遗传构成与其环境暴露记录（暴露组）之间的相互作用被认为是人类恶性肿瘤的重要决定因素。最近的证据强调了表观遗传机制在介导基因-环境相互作用以及将暴露转化为肿瘤发生中的关键作用。越来越多的证据表明，表观遗传变化可能是特定的风险因素（“指纹”），这将有助于发现癌症的新生物标志物。在这里，我们回顾了与环境刺激和癌症风险相关的表观遗传学的科学现状，强调了该领域的关键进展。讨论了关键的知识差距和研究需求，以及表观基因组学的进展，这可能有助于理解表观遗传改变的功能相关性。讨论了将表观遗传变化与暴露和癌症联系起来的因果推断所需的关键要素，以及如何将这些变化纳入致癌物评估以及理解环境引起表观基因组失调的机制。
