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表观遗传学与癌症:迈向对环境和饮食因素影响的评估

Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors.

作者信息

Herceg Zdenko

机构信息

Epigenetics Team, Molecular Carcinogenesis and Biomarkers Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, F-69008, Lyon, France.

出版信息

Mutagenesis. 2007 Mar;22(2):91-103. doi: 10.1093/mutage/gel068. Epub 2007 Feb 6.

Abstract

While the field of cancer genetics has enjoyed a great deal of attention among cancer researchers in the last few decades, the appreciation of cancer epigenetics is more recent, -owing to the fact that epigenetic mechanisms have emerged as key mechanisms in cancer development. All critical changes in cancer cells, such as silencing of tumour-suppressor genes, activation of oncogenes and defects in DNA repair, are caused not only by genetic but also by epigenetic mechanisms. Epigenetic events can affect many steps in tumour development; therefore, better understanding of epigenetic mechanisms is fundamental to our ability to successfully prevent, diagnose and treat cancer. Various environmental and dietary agents and lifestyles are suspected to be implicated in the development of a wide range of human cancers by eliciting epigenetic changes, though the contribution of epigenetic mechanisms to a given human cancer type and the precise targets of epigenetic alterations during cancer development are largely unknown. The major obstacle in establishing a relationship between epigenetic changes and exposure to dietary, lifestyle and environmental factors and cancer is the fact that studies are typically too small and lack statistical power to identify the interactions between epigenetic changes and exposures. Tremendous advances in our understanding of basic epigenetic mechanisms and rapid progress that is being made in developing new powerful technologies, such as those for sensitive and quantitative detection of epigenetic changes as well as for genome-wide analysis (epigenomics), hold great promise that these issues may be addressed in near future. Therefore, experimental evidence on the precise role of epigenetic changes induced by environment, diet and lifestyle is eagerly awaited.

摘要

在过去几十年里,癌症遗传学领域备受癌症研究人员的广泛关注,而对癌症表观遗传学的认识则相对较新,这是因为表观遗传机制已成为癌症发展的关键机制。癌细胞中的所有关键变化,如肿瘤抑制基因的沉默、癌基因的激活以及DNA修复缺陷,不仅由遗传机制引起,也由表观遗传机制导致。表观遗传事件可影响肿瘤发展的多个步骤;因此,更好地理解表观遗传机制对于我们成功预防、诊断和治疗癌症的能力至关重要。尽管表观遗传机制对特定人类癌症类型的贡献以及癌症发展过程中表观遗传改变的确切靶点在很大程度上尚不清楚,但各种环境和饮食因素以及生活方式被怀疑通过引发表观遗传变化而与多种人类癌症的发生有关。在确定表观遗传变化与饮食、生活方式和环境因素暴露以及癌症之间的关系方面,主要障碍在于研究通常规模太小,缺乏统计学效力来识别表观遗传变化与暴露之间的相互作用。我们对基本表观遗传机制的理解取得了巨大进展,并且在开发新的强大技术方面也取得了快速进展,例如用于敏感和定量检测表观遗传变化以及全基因组分析(表观基因组学)的技术,这使得有望在不久的将来解决这些问题。因此,人们急切期待有关环境、饮食和生活方式诱导的表观遗传变化的确切作用的实验证据。

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