Role of folate in colon cancer development and progression
Role of folate in colon cancer development and progression
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DOI：
10.1093/jn/133.11.3731s
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发表时间：
2003-11-01
影响因子：
4.2
通讯作者：
Kim, YI
中科院分区：
文献类型：
--
作者：
Kim, YI
叶酸是一种水溶性B族维生素，是1-碳转移的重要辅助因子，是一种重要的营养因子，可能调节结直肠癌的发生。流行病学和临床研究表明，膳食叶酸摄入量和血液叶酸水平与结直肠癌风险呈负相关。总的来说，这些研究表明，与摄入量最低的人相比，膳食叶酸摄入量最高的人患结直肠癌的风险降低了40%。使用化学和遗传易感啮齿动物模型的动物研究为叶酸消耗和结直肠癌发生之间的因果关系以及叶酸补充剂的剂量依赖性保护作用提供了相当大的支持。然而，动物研究也表明，叶酸干预的剂量和时间是至关重要的，在提供安全和有效的化学预防;异常高的补充叶酸水平和叶酸干预后，显微镜下肿瘤病灶建立在结直肠粘膜促进而不是抑制结直肠癌的发生。这些动物研究结合临床观察表明，叶酸对致癌作用具有双重调节作用，这取决于叶酸干预的时间和剂量。叶酸缺乏具有抑制作用，而叶酸补充剂对已建立的肿瘤的进展具有促进作用。相反，正常上皮组织中的叶酸缺乏似乎使它们易于发生肿瘤转化，并且适度水平的叶酸补充抑制正常组织中肿瘤的发展。尽管与动物模型相关的限制，这些动物研究表明，叶酸干预的最佳时机和剂量需要建立安全和有效的化学预防人类。
Folate, a water-soluble B vitamin and important cofactor in 1-carbon transfer, is an important nutritional factor that may modulate the development of colorectal cancer. Epidemiologic and clinical studies indicate that dietary folate intake and blood folate levels are inversely associated with colorectal cancer risk. Collectively, these studies suggest an similar to40% reduction in the risk of colorectal cancer in individuals with the highest dietary folate intake compared with those with the lowest intake. Animal studies using chemical and genetically predisposed rodent models have provided considerable support for a causal relationship between folate depletion and colorectal carcinogenesis as well as a dose-dependent protective effect of folate supplementation. However, animal studies have also shown that the dose and timing of folate intervention are critical in providing safe and effective chemoprevention; exceptionally high supplemental folate levels and folate intervention after microscopic neoplastic foci are established in the colorectal mucosa promote rather than suppress colorectal carcinogenesis. These animal studies in conjunction with clinical observations suggest that folate possesses the dual modulatory effects on carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect whereas folate supplementation has a promoting effect on progression of established neoplasms. In contrast, folate deficiency in normal epithelial tissues appears to predispose them to neoplastic transformation, and modest levels of folate supplementation suppress the development of tumors in normal tissues. Notwithstanding the limitations associated with animal models, these animal studies suggest that the optimal timing and dose of folate intervention need to be established for safe and effective chemoprevention in humans.