Epidemiologic studies of folate and colorectal neoplasia: a review
Epidemiologic studies of folate and colorectal neoplasia: a review
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DOI：
10.1093/jn/132.8.2350s
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Giovannucci, E
中科院分区：
文献类型：
--
作者：
Giovannucci, E
膳食叶酸影响DNA甲基化，合成和修复。这些DNA过程中的畸变可能会增强癌变，特别是在快速增殖的组织如结直肠粘膜中。DNA甲基化异常可能影响癌症相关基因的表达，叶酸水平不足可能导致尿嘧啶错误掺入DNA和染色体断裂。叶酸缺乏在几种动物模型中增强肠道癌的发生。越来越多的流行病学研究表明，从饮食来源或补充剂中摄入更多的叶酸可能会降低结直肠腺瘤和癌症的风险。更有限的数据也表明，饮食中的蛋氨酸，也可能影响甲基化，可能有类似的保护作用。大量饮酒具有很强的抗叶酸作用，也与结直肠肿瘤的高风险有关。当叶酸或甲硫氨酸摄入量低时，酒精的有害作用会加重。一些证据还表明，结直肠肿瘤的风险可能会根据亚甲基四氢叶酸还原酶（一种参与叶酸代谢的酶）的遗传多态性而变化。累积数据表明，保持足够的叶酸水平可能对降低结直肠癌风险很重要。
Dietary folate influences DNA methylation, synthesis and repair. Aberrations in these DNA processes may enhance carcinogenesis, particularly in rapidly proliferative tissues such as the colorectal mucosa. DNA methylation abnormalities may influence the expression of cancer-related genes, and inadequate levels of folate may lead to uracil misincorporation into DNA and to chromosomal breaks. Folate deficiency enhances intestinal carcinogenesis in several animal models. An increasing number of epidemiologic studies indicate that higher intakes of folate either from dietary sources or from supplements may lower the risk of colorectal adenoma and cancer. More limited data also suggest that dietary methionine, which might also influence methylation, may have a similar protective role. High alcohol consumption, which has a strong antifolate effect, also has been related to higher risk of colorectal neoplasia. The deleterious effects of alcohol are accentuated when folate or methionine intake is low. Some evidence also suggests that the risk of colorectal neoplasia may vary according to genetic polymorphisms in methylenetetrahydrofolate reductase, an enzyme that is involved in folate metabolism. The cumulative data indicate that maintaining adequate folate levels may be important in lowering risk of colorectal cancer.