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Epigenetics:研究发现衰老增加乳腺癌患病风险的“原罪”

  1. 乳腺癌
  2. 甲基化
  3. 衰老

来源:生物谷 2013-11-23 11:15

2013年11月23日讯 /生物谷BIOON/--近日,研究人员发现,与无病变乳腺组织老化有关的DNA表观遗传学改变,在乳腺肿瘤中会进一步发生变化。这一发现将发表在2014年2月的Epigenetics杂志上,研究通过识别存在于正常老化乳腺组织中的表遗传学改变,说明癌症和衰老是如何紧密相互联系的过程,以及提示:正常老化乳腺组织中的表遗传学改变可能会增加癌症风险。

表观遗传的改变表现为DNA甲基化的不同模式,后者涉及DNA的化学改性。而DNA甲基化是一种正常的和必要的表观遗传过程,与正常乳腺组织相比,乳腺癌中甲基化模式发生明显改变。因此,非典型的DNA甲基化被认为在癌症发生前就存在。

在这项研究中,研究人员利用可公开获得的无病变乳腺组织全基因组甲基化数据,识别与老化过程相关的甲基化改变。将甲基化在正常组织中的变化水平与乳腺肿瘤组织中甲基化变化水平比较,其中发现在乳腺癌肿,与老化相关的甲基化变化进一步发生变化。

其数据表明,在无病变乳腺组织向癌症发展过程中,随时间的发展,有可能一些常见的基因组区域在DNA甲基化过程中特别容易发生变化。虽然衰老是乳腺癌最主要的危险因素之一,但衰老如何增加女性患乳腺癌风险的相关机制尚未完全阐明。

新兴的文献资料表明,衰老可能对DNA甲基化模式产生深远的影响,这或许就是衰老是乳腺癌风险增加的原因。因此,本研究进一步分析了乳腺癌危险因素如衰老促发癌变的生物学机制。(生物谷Bioon.com)

Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation

Kevin C Johnson, Devin C Koestler, Chao Cheng, Brock C Christensen

Age is a key risk factor for breast cancer and epigenetic alterations may contribute to age-related increases in breast cancer risk, though the relation of age-related methylation in normal breast tissues with altered methylation in breast tumors is unclear. We investigated the relation of age with DNA methylation in normal breast tissues genome-wide using two data sets from the Gene Expression Omnibus (GEO) database (GSE32393 and GSE31979). We validated our observations in an independent set of normal breast tissues, examined age-related methylation in normal breast for enrichment of genomic features, and compared age-related methylation in normal tissue with methylation alterations in breast tumors. Between the two array-based methylation data sets, there were 204 CpG loci with significant (P < 0.05) and consistent age-related methylation, 97% of which were increases in methylation. Our validation sets confirmed the direction of age-related DNA methylation changes in all measured regions. Among the 204 age-related CpG loci, we observed a significant enrichment for CpG islands (P = 8.7E-6) and polycomb group protein target genes (P = 0.03). In addition, 24 of the 204 CpGs with age-related methylation in normal breast were significantly differentially methylated between normal and breast tumor tissues. We identified consistent age-related methylation changes in normal breast tissue that are further altered in breast tumors and may represent early events contributing to breast carcinogenesis. This work identifies age-related methylation in normal breast tissue and begins to deconstruct the contribution of aging to epigenetic alterations present in breast tumors.

 

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