ABSTRACT
Contents 9.1 Introduction ........................................................................................... 208 9.2 Epigenetics and cancer ......................................................................... 209 9.3 Dietary exposure in utero: Agouti model ..........................................211 9.4 Methyl-deficient diet induced hepatocarcinogenesis ...................... 213 9.5 Dietary polyphenols reactivate silenced
genes via epigenetic mechanisms .......................................................214 9.6 Histone deacetylase (HDAC) inhibition by dietary factors .............216 9.7 Dietary modulation of polycomb repressive complexes ................. 218 9.8 Epigenome mapping to identify targets of dietary exposure ........ 220 9.9 Conclusions ............................................................................................ 221 References ........................................................................................................ 222
Compelling evidence suggests that diet and dietary factors are important in cancer etiology by inhibiting or enhancing the cancer process. Because diet may contribute significantly to thecausation of many human cancers, it is important to uncoverthe molecular mechanisms of action of dietary bioactive factors in cancer prevention, as well as those stimulating neoplastic cell transformations. The role of epigenetic mechanisms in the etiology of disease, including cancer development and progression, has been increasingly recognized in recent years. The importance of epigenetic mechanisms is highlighted by their influence on gene expression and chromatin stability, which thereby impact the regulation of cell cycle control, DNA damage, apoptosis, differentiation, and other cancer-related processes. Evidence suggests that environmental factors, such as diet, may be significant regulators of epigenetic events, including DNA methylation and histone posttranslational modulation. For example, it has long been known that folate participates in the generation of S-adenosylmethionine, which acts as a methyl donor in the methylation of cytosines in DNA and participates in posttranslational methylation
of histones. A classic example for the role of diet in epigenetics and cancer is the finding that dietary methyl deficiency (folate, choline, and methionine) in a rat model has been shown to alter hepatic DNA methylation patterns and induce hepatocarcinogenesis in the absence of a carcinogen. Several other bioactive food components (BFCs), including genistein, epigallocatechin gallate, diallyl disulfide, and sulforaphane have been suggested to impact epigenetic mechanisms. Many of these examples will be presented, as well as the next steps in diet, epigenetic events, and cancer prevention research.
