Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer
Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer
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DOI：
10.1093/jn/135.12.2960s
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Powers, HJ
中科院分区：
文献类型：
--
作者：
Powers, HJ
流行病学研究表明，叶酸摄入量低与上皮性癌症（包括结肠直肠癌和宫颈癌）的风险增加有关。核黄素受到的关注要少得多，但人们对黄素在叶酸代谢中的作用以及这两种维生素之间可能的协同保护作用越来越感兴趣。叶酸在DNA合成、修复和甲基化中起着关键作用，这构成了叶酸在癌症预防中假定作用的机制解释的基础。叶酸在这些过程中的作用可能受到亚甲基四氢叶酸还原酶（MTHFR）常见的C677T耐热变异体基因型的调节，其纯合性与酶活性降低、血浆和红细胞叶酸降低以及血浆同型半胱氨酸升高有关。作为FAD的核黄素是MTHFR的辅助因子，在测定血浆同型半胱氨酸（叶酸状态的功能标记物）时，核黄素状态、叶酸状态和基因型之间存在明显的相互作用。MTHFR C677T多态性似乎与叶酸和核黄素相互作用，以一种根据癌症部位不同的方式调节癌症风险。大多数证据表明，这种多态性对结直肠癌的风险有保护作用，但对宫颈癌风险的影响尚不清楚。这种多态性对癌症风险的影响似乎受到其他因素的进一步调节，包括酒精，在宫颈癌的情况下，感染人类乳头瘤病毒。决定饮食和基因型相互作用对癌症风险影响的另一个因素可能是癌症发展的阶段。
Epidemiological studies have linked low folate intake with an increased risk of epithelial cancers, including colorectal cancer and cervical cancer. Riboflavin has received much less attention, but there is increasing interest in the well-established role that flavins play in folate metabolism and the possible synergy of a protective effect between these 2 vitamins. Folate plays a key role in DNA synthesis, repair, and methylation, and this forms the basis of mechanistic explanations for a putative role for folate in cancer prevention. The role of folate in these processes may be modulated by genotype for the common C677T thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), homozygosity for which is associated with lower enzyme activity, lower plasma and red blood cell folate, and elevated plasma homocysteine. Riboflavin, as FAD, is a cofactor for MTHFR and there is evidently some interaction among riboflavin status, folate status, and genotype in determining plasma homocysteine, a functional marker of folate status. The MTHFR C677T polymorphism appears to interact with folate and riboflavin in modulating cancer risk in a manner that varies according to cancer site. Most evidence points to a protective effect of this polymorphism for risk of colorectal cancer, but the effect on cervical cancer risk is not clear. The effect of this polymorphism on cancer risk seems to be further modulated by other factors, including alcohol and, in the case of cervical cancer, infection with the human papilloma virus. An additional factor determining the effect of diet and genotype interactions on cancer risk may be the stage of cancer development.