a Department of Hematology and Oncology , Institute of Clinical Medicine, University of Tartu , Tartu , Estonia.
Drug Metab Rev. 2017 Feb;49(1):56-83. doi: 10.1080/03602532.2016.1258075. Epub 2016 Nov 23.
Catechol-O-methyltransferase, COMT, is an important phase II enzyme catalyzing the transfer of a methyl-group from S-adenosylmethionine to a catechol-containing substrate molecule. A genetic variant Val158Met in the COMT gene leads to a several-fold decrease in the enzymatic activity giving rise to the accumulation of potentially carcinogenic endogenous catechol estrogens and their reactive intermediates and increasing thus the risk of tumorigenesis. However, numerous association studies between the COMT genotype and susceptibility to various malignancies have shown inconsistent and controversial findings indicating that additional gene-gene and gene-environment interactions might be crucial in modulating the physiological role of the COMT. In this review article, the important contribution of dietary catechol-containing flavonoids to modification of the relationships between the COMT genotype and cancer risk is discussed. Whereas, the diverse anticancer activities of common phytochemicals, such as green tea polyphenols, quercetin, fisetin or luteolin, can be markedly changed (both decreased or increased) by the COMT-mediated O-methylation of these exogenous substrates, flavonoids can also behave as potent inhibitors of the COMT enzyme slowing detoxification of endogenous catechol estrogens. Such a many-featured functioning of the COMT and its complex regulation by several different genetic and environmental factors, including plant-based food ingredients, emphasizes the necessity to further stratify the association studies between the COMT genotype and tumor risk by consumption of catechol-containing dietary flavonoids. Currently, it can be only speculated that some of the possible associations might be masked by the regular intake of specific food polyphenols, taking effect in certain communities or populations.
儿茶酚-O-甲基转移酶（COMT）是一种重要的 II 相酶，可催化 S-腺苷甲硫氨酸向含有儿茶酚的底物分子转移一个甲基。COMT 基因中的遗传变异 Val158Met 导致酶活性降低几倍，导致潜在致癌的内源性儿茶酚雌激素及其反应性中间产物的积累，从而增加肿瘤发生的风险。然而，许多关于 COMT 基因型与各种恶性肿瘤易感性的关联研究表明，存在不一致和有争议的发现，表明额外的基因-基因和基因-环境相互作用可能在调节 COMT 的生理作用方面至关重要。在这篇综述文章中，讨论了膳食中含有儿茶酚的类黄酮对修饰 COMT 基因型与癌症风险之间关系的重要贡献。虽然常见植物化学物质（如绿茶多酚、槲皮素、漆黄素或木犀草素）的多种抗癌活性可以通过 COMT 介导的这些外源性底物的 O-甲基化而明显改变（降低或增加），但类黄酮也可以作为儿茶酚雌激素内源性解毒的有效抑制剂。COMT 的这种多功能作用及其受多种不同遗传和环境因素（包括植物性食物成分）的复杂调节，强调了进一步对 COMT 基因型与肿瘤风险之间的关联研究进行分层的必要性，这些研究涉及到含有儿茶酚的饮食类黄酮的摄入。目前，只能推测一些可能的关联可能会被特定食物多酚的规律摄入所掩盖，这些多酚在某些社区或人群中发挥作用。
