Folate and carcinogenesis: An integrated scheme
Folate and carcinogenesis: An integrated scheme
复制标题
DOI：
10.1093/jn/130.2.129
复制
发表时间：
2000-02-01
影响因子：
4.2
通讯作者：
Mason, JB
中科院分区：
文献类型：
--
作者：
Choi, SW;Mason, JB
总的来说，来自流行病学、动物和人类研究的证据强烈表明，叶酸状态可以调节特定组织患癌症的风险，其中最值得注意的是结直肠。叶酸缺乏似乎会增强致癌作用，而叶酸补充量高于目前被认为是基本需求的水平似乎会产生保护作用。这种癌症风险调节的介导方式尚不清楚，但已经描述了几种可能的机制。叶酸在通用甲基供体 S-腺苷甲硫氨酸的形成以及 DNA 和 RNA 的嘌呤和胸苷合成的形成中发挥着重要作用。因此，迄今为止进行的大多数机制研究都集中在 DNA 甲基化的改变、DNA 完整性的破坏和 DNA 修复的破坏上，所有这些都在叶酸消耗时观察到。人们相信DNA中的这些畸变通过改变关键肿瘤抑制基因和原癌基因的表达来增强致癌作用。最近，亚甲基四氢叶酸还原酶基因的常见多态性的作用也得到了强调。本综述介绍了最有可能解释叶酸作用的机制，并提出了一个综合方案来解释这些机制如何相互作用。
Collectively, the evidence from epidemiologic, animal and human studies strongly suggests that folate status modulates the risk of developing cancers in selected tissues, the most notable of which is the colorectum. Folate depletion appears to enhance carcinogenesis whereas folate supplementation above what is presently considered to be the basal requirement appears to convey a protective effect. The means by which this modulation of cancer risk is mediated is not known with certainty, but there are several plausible mechanisms which have been described. Folate plays a major role in the formation of S-adenosylmethionine, the universal methyl donor, as well as in the formation of purine and thymidine synthesis for DNA and RNA. Therefore, most mechanistic studies performed to date have focused on alterations in DNA methylation, disruption of DNA integrity and disruption of DNA repair, all of which have been observed with folate depletion. These aberrations in DNA are believed to enhance carcinogenesis by altering the expression of critical tumor suppressor genes and proto-oncogenes. Recently, the role of a common polymorphism of the methylenetetrahydrofolate reductase gene has been highlighted as well. This review presents those mechanisms which are the most likely candidates to explain folate's effects and it proposes an integrated scheme to explain how these mechanisms might interact.