Department of Pharmacology and Toxicology, Dartmouth Medical School, 7650 Remsen, Hanover, NH 03755, USA.
Adv Exp Med Biol. 2013;754:233-52. doi: 10.1007/978-1-4419-9967-2_12.
The importance of somatic epigenetic alterations in tissues targeted for carcinogenesis is now well recognized and considered a key molecular step in the development of a tumor. Particularly, alteration of gene-specific and genomic DNA methylation has been extensively characterized in tumors, and has become an attractive biomarker of risk due to its specificity and stability in human samples. It also is clear that tumors do not develop as isolated phenomenon in their target tissue, but instead result from altered processes affecting not only the surrounding cells and tissues, but other organ systems, including the immune system. Thus, alterations to DNA methylation profiles detectable in peripheral blood may be useful not only in understanding the carcinogenic process and response to environmental insults, but can also provide critical insights in a systems biological view of tumorigenesis. Research to date has generally focused on how environmental exposures alter genomic DNA methylation content in peripheral blood. More recent work has begun to translate these findings to clinically useful endpoints, by defining the relationship between DNA methylation alterations and cancer risk. This chapter highlights the existing research linking the environment, blood-derived DNA methylation alterations, and cancer risk, and points out how these epigenetic alterations may be contributing fundamentally to carcinogenesis.
体细胞表观遗传改变在致癌作用的目标组织中具有重要意义，现在已被广泛认可，并被认为是肿瘤发生的关键分子步骤。特别是，基因特异性和基因组 DNA 甲基化的改变在肿瘤中得到了广泛的描述，并且由于其在人类样本中的特异性和稳定性，已成为一种有吸引力的风险生物标志物。同样清楚的是，肿瘤并非在其目标组织中孤立地发展，而是源于改变了的过程，这些过程不仅影响周围的细胞和组织，而且还影响其他器官系统，包括免疫系统。因此，在外周血中可检测到的 DNA 甲基化谱的改变不仅有助于了解致癌过程和对环境损伤的反应，而且还可以从肿瘤发生的系统生物学角度提供关键的见解。迄今为止的研究主要集中在环境暴露如何改变外周血中的基因组 DNA 甲基化含量上。最近的工作开始将这些发现转化为临床有用的终点，通过定义 DNA 甲基化改变与癌症风险之间的关系。本章重点介绍了将环境、血液来源的 DNA 甲基化改变与癌症风险联系起来的现有研究，并指出这些表观遗传改变如何从根本上促进致癌作用。
