Ong Thomas Prates, Moreno Fernando Salvador, Ross Sharon Ann
Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
J Nutrigenet Nutrigenomics. 2011;4(5):275-92. doi: 10.1159/000334585. Epub 2012 Feb 22.
Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated.
表观遗传过程参与癌症发展,并可能影响癌症预防。全基因组DNA低甲基化、基因启动子高甲基化以及异常的组蛋白翻译后修饰是肿瘤细胞的特征,这些特征与基因组不稳定和基因表达改变有关。由于表观遗传失调在致癌过程早期就会出现,并且具有潜在的可逆性,因此有人提出针对表观基因组的干预策略用于癌症预防。具有抗癌潜力的生物活性食品成分(BFCs),包括叶酸、多酚、硒、类维生素A、脂肪酸、异硫氰酸盐和烯丙基化合物,会影响DNA甲基化和组蛋白修饰过程。这些活性已被证明会影响参与细胞增殖、死亡和分化的基因的表达,而这些基因在癌症中经常发生改变。尽管表观基因组是BFCs用于癌症预防的一个有前景的靶点,但很少有研究探讨饮食成分在体内对这些机制的影响,特别是对人类表型的影响,因此饮食介导癌症预防作用的确切机制仍不清楚。需要阐明的主要因素包括BFCs产生表观遗传效应的有效剂量和给药时间。由于饮食与表观基因组的相互作用可能在子宫内就会发生,因此应进一步研究早期营养对癌症风险编程的影响。