Catechol-O-methyltransferase: characteristics, polymorphisms and role in breast cancer

Drug discovery today. Disease mechanisms Pub Date : 2012-06-01 DOI:10.1016/j.ddmec.2012.10.002

James D. Yager

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引用次数: 42

Abstract

Catechol estrogens are carcinogenic, probably because of their estrogenicity and potential for further oxidative metabolism to reactive quinones. Estrogenic quinones cause oxidative DNA damage as well as form mutagenic depurinating adenine and guanine adducts. O-Methylation by catechol-O-methyltransferase (COMT) blocks their estrogenicity and prevents their oxidation to quinones. A single gene encodes both membrane bound (MB) and soluble (S) forms of COMT. The COMT gene contains 34 single nucleotide polymorphisms (SNPs). The valine108 (S-COMT)/158 (MB-COMT) SNP encodes a low activity form of COMT and has been widely studied as a putative risk factor for breast cancer, with inconsistent results. Investigations of two other SNPs in the promoter of MB-COMT that may affect its expression have also provided mixed results. Future studies on the role of COMT in breast cancer should incorporate measurement of biomarkers that reflect COMT activity and its protective effects.

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儿茶酚- o -甲基转移酶:特征、多态性及其在乳腺癌中的作用

儿茶酚类雌激素具有致癌性，可能是因为它们的雌激素性和进一步氧化代谢成活性醌的潜力。雌激素醌引起DNA氧化损伤，并形成致突变的去嘌呤和鸟嘌呤加合物。儿茶酚- o -甲基转移酶(COMT)的o -甲基化阻断了它们的雌激素性，阻止了它们氧化成醌。一个基因编码膜结合(MB)和可溶性(S)形式的COMT。COMT基因含有34个单核苷酸多态性(snp)。valine108 (S-COMT)/158 (MB-COMT) SNP编码一种低活性形式的COMT，作为一种假定的乳腺癌危险因素被广泛研究，但结果不一致。对MB-COMT启动子中可能影响其表达的另外两个snp的研究也提供了不同的结果。未来关于COMT在乳腺癌中的作用的研究应纳入反映COMT活性及其保护作用的生物标志物的测量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Drug discovery today. Disease mechanisms

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