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探究豆浆暴露后人体乳腺 DNA 甲基化谱

Exploratory analysis of the human breast DNA methylation profile upon soymilk exposure.

机构信息

Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, Belgium, Coupure Links 653, B-9000, Ghent, Belgium.

Bioinformatics Institute Ghent: from Nucleotides 2 Networks (BIG-N2N), Ghent University, Belgium, Ghent University - VIB, Technologiepark 927, B-9052, Ghent, Belgium.

出版信息

Sci Rep. 2018 Sep 11;8(1):13617. doi: 10.1038/s41598-018-31767-x.

DOI:10.1038/s41598-018-31767-x
PMID:30206342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6133922/
Abstract

Upon soy consumption, isoflavone metabolites attain bioactive concentrations in breast tissue possibly affecting health. Though in vitro epigenetic activity of soy metabolites has been described, the in vivo impact on the epigenome is largely unknown. Therefore, in this case-control study, the breast glandular tissue DNA methylome was explored in women undergoing an aesthetic breast reduction. After a run-in phase, 10 generally healthy Belgian or Dutch women received soymilk for 5 days. MethylCap-seq methylation profiles were compared with those of 10 matched controls. Isoflavones and their microbial metabolites were quantified in urine, serum, and glandular breast tissue (liquid chromatography-mass spectrometry) and 17β-estradiol in glandular breast tissue (immunoassay). Global DNA methylation levels were obtained for 6 cases and 5 controls using liquid chromatography-mass spectrometry. Although lower MethylCap-seq coverages were observed, mass spectrometry results and computational LINE-1 methylation analysis did not provide evidence supporting global methylation alterations upon treatment. At a false discovery rate of 0.05, no differentially methylated loci were identified. Moreover, a set of previously identified loci was specifically tested, but earlier reported results could not be validated. In conclusion, after a 5-day soymilk treatment, no major general epigenetic reprogramming in breast tissue could be found in this exploratory study.

摘要

摄入大豆后,大豆异黄酮代谢物在乳腺组织中达到生物活性浓度,可能会影响健康。虽然已经描述了大豆代谢物的体外表观遗传活性,但它们对表观基因组的体内影响在很大程度上尚不清楚。因此,在这项病例对照研究中,我们探索了接受美容乳房缩小术的女性的乳腺组织 DNA 甲基组。在适应期后,10 名通常健康的比利时或荷兰女性连续 5 天饮用豆浆。通过 MethylCap-seq 比较了代谢物组与 10 名匹配对照的甲基化谱。通过液相色谱-质谱法(LC-MS)对尿液、血清和乳腺组织中的大豆异黄酮及其微生物代谢物进行了定量,对乳腺组织中的 17β-雌二醇进行了免疫测定。通过液相色谱-质谱法(LC-MS)对 6 例和 5 例对照获得了全基因组 DNA 甲基化水平。尽管观察到较低的 MethylCap-seq 覆盖率,但质谱结果和计算 LINE-1 甲基化分析并未提供支持治疗后全基因组甲基化改变的证据。在错误发现率为 0.05 的情况下,未鉴定出差异甲基化基因座。此外,还专门测试了一组先前确定的基因座,但先前报道的结果无法得到验证。总之,在为期 5 天的豆浆治疗后,这项探索性研究未发现乳腺组织中主要的普遍表观遗传重编程。

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本文引用的文献

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Dietary Isoflavones and Breast Cancer Risk.膳食异黄酮与乳腺癌风险
Medicines (Basel). 2017 Apr 7;4(2):18. doi: 10.3390/medicines4020018.
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Methylome analysis of extreme chemoresponsive patients identifies novel markers of platinum sensitivity in high-grade serous ovarian cancer.对极端化疗反应患者的甲基化组分析确定了高级别浆液性卵巢癌铂敏感性的新标志物。
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