Yager James D
Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States.
Drug Discov Today Dis Mech. 2012 Jun 1;9(1-2):e41-e46. doi: 10.1016/j.ddmec.2012.10.002.
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. -Methylation by catechol--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.
儿茶酚雌激素具有致癌性，可能是由于其雌激素活性以及进一步氧化代谢为反应性醌类的可能性。雌激素醌类会导致氧化性DNA损伤，并形成诱变的脱嘌呤腺嘌呤和鸟嘌呤加合物。儿茶酚-O-甲基转移酶（COMT）进行的甲基化会阻断其雌激素活性，并防止其氧化为醌类。单个基因编码膜结合（MB）和可溶性（S）两种形式的COMT。COMT基因包含34个单核苷酸多态性（SNP）。缬氨酸108（S-COMT）/158（MB-COMT）单核苷酸多态性编码一种低活性形式的COMT，作为乳腺癌的假定风险因素已得到广泛研究，但结果并不一致。对MB-COMT启动子中另外两个可能影响其表达的单核苷酸多态性的研究也得出了不一致的结果。未来关于COMT在乳腺癌中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。
