Department of Oncology, Human Nutrition Unit, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield S10 2RX, UK.
Proc Nutr Soc. 2012 Nov;71(4):592-7. doi: 10.1017/S0029665112000717. Epub 2012 Aug 6.
Diet is a major factor in the aetiology of colorectal cancer (CRC). Epidemiological evidence suggests that folate confers a modest protection against CRC risk. However, the relationship is complex, and evidence from human intervention trials and animal studies suggests that a high-dose of folic acid supplementation may enhance the risk of colorectal carcinogenesis in certain circumstances. The molecular mechanisms underlying the apparent dual modulatory effect of folate on colorectal carcinogenesis are not fully understood. Folate is central to C1 metabolism and is needed for both DNA synthesis and DNA methylation, providing plausible biological mechanisms through which folate could modulate cancer risk. Aberrant DNA methylation is an early event in colorectal carcinogenesis and is typically associated with the transcriptional silencing of tumour suppressor genes. Folate is required for the production of S-adenosyl methionine, which serves as a methyl donor for DNA methylation events; thereby folate availability is proposed to modulate DNA methylation status. The evidence for an effect of folate on DNA methylation in the human colon is limited, but a modulation of DNA methylation in response to folate has been demonstrated. More research is required to clarify the optimum intake of folate for CRC prevention and to elucidate the effect of folate availability on DNA methylation and the associated impact on CRC biology.
饮食是结直肠癌（CRC）病因学中的一个主要因素。流行病学证据表明，叶酸对 CRC 风险有一定的保护作用。然而，这种关系很复杂，来自人体干预试验和动物研究的证据表明，在某些情况下，高剂量叶酸补充可能会增加结直肠致癌的风险。叶酸对结直肠致癌作用的明显双重调节作用的分子机制尚未完全阐明。叶酸是 C1 代谢的核心，是 DNA 合成和 DNA 甲基化所必需的，为叶酸可能通过调节癌症风险提供了合理的生物学机制。异常的 DNA 甲基化是结直肠癌变的早期事件，通常与肿瘤抑制基因的转录沉默相关。叶酸是 S-腺苷甲硫氨酸产生所必需的，S-腺苷甲硫氨酸作为 DNA 甲基化事件的甲基供体；因此，叶酸的可用性被认为可以调节 DNA 甲基化状态。叶酸对人结肠中 DNA 甲基化的影响证据有限，但已经证明叶酸可以调节 DNA 甲基化。需要进一步的研究来阐明预防 CRC 所需的最佳叶酸摄入量，并阐明叶酸可用性对 DNA 甲基化的影响及其对 CRC 生物学的关联影响。
