乳腺癌患者社会经济地位和肿瘤DNA甲基化的全表观基因组分析。

IF 5.7 2区 医学 Q1 Medicine
Jianhong Chen, Mark D Long, Sirinapa Sribenja, Sung Jun Ma, Li Yan, Qiang Hu, Song Liu, Thaer Khoury, Chi-Chen Hong, Elisa Bandera, Anurag K Singh, Elizabeth A Repasky, Elizabeth G Bouchard, Michael Higgins, Christine B Ambrosone, Song Yao
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引用次数: 1

摘要

背景:不利的社会经济地位(SEP),包括较低的受教育程度和家庭收入,可能影响癌症的风险和预后。我们假设DNA甲基化可以作为一种中介表观遗传机制,内化和反映sep的生物学影响。方法:基于来自妇女健康圈研究中694名乳腺癌患者的Illumina 450 K阵列的肿瘤DNA甲基化数据,我们进行了与受教育程度和家庭收入相关的表观基因组分析。利用公开数据库中的数据,在计算机上探索了已确定的CpG位点的功能影响。结果:我们确定了25个与家庭收入相关的CpG位点,但没有一个与受教育程度相关。两个CpG位点cg00452016和cg01667837分别位于NNT和GPR37的启动子区域,在每个区域都发现了多个表观遗传调控特征。NNT参与β-肾上腺素能应激信号和炎症反应,而GPR37参与神经和免疫反应。对于这两个基因座,基因表达与DNA甲基化水平呈负相关。这种关联在黑人和白人妇女之间是一致的,并且没有因肿瘤雌激素受体(ER)状态而不同。结论:在大量乳腺癌患者人群中,我们发现了家庭收入对肿瘤DNA甲基化组的显著生物学影响的证据,包括β-肾上腺素能应激和免疫反应途径中的基因。我们的研究结果支持社会经济地位对肿瘤组织的生物学效应,这可能与癌症的发生和进展有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

Background: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.

Methods: Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women's Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases.

Results: We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status.

Conclusions: In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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