Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis.
Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis.
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DOI：
10.3109/07420528.2011.618896
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发表时间：
2011-12
影响因子：
2.8
通讯作者：
Hansen J
中科院分区：
文献类型：
--
作者：
Zhu Y;Stevens RG;Hoffman AE;Tjonneland A;Vogel UB;Zheng T;Hansen J
表观遗传关联研究表明，与无癌对照组相比，乳腺癌病例中核心昼夜节律基因的启动子甲基化存在差异。目前的试点研究旨在调查影响乳腺癌风险的表观遗传变化是否可能是由于夜间暴露在光线下造成的昼夜节律紊乱引起的。这项研究包括从丹麦进行的前瞻性队列中 117 名女性受试者的全血中提取的存档 DNA 样本。基于聚合酶链反应 (PCR) 的方法用于检测基因启动子甲基化，而全基因组甲基化分析则使用 Illumina Infinium 甲基化芯片进行。长期轮班工作导致相同的 CLOCK 启动子低甲基化和 CRY2 高甲基化，正如之前在乳腺癌病例对照研究中观察到的那样。全基因组甲基化分析进一步发现轮班工人普遍存在甲基化改变，包括许多甲基化和癌症相关基因的变化。对甲基化模式改变的基因的通路分析揭示了几种与癌症相关的通路。生成的前三个网络之一被指定为“DNA 复制、重组和修复、基因表达、行为”，其中 ESR1（雌激素受体 α）在该网络中最为突出，强调了长期轮班工人中差异甲基化的基因与乳腺癌的潜在相关性。这些结果虽然是探索性的，但却首次证明了夜班工作与癌症相关的表观遗传效应，值得进一步研究。考虑到全世界有数以百万计的轮班工人，了解这种暴露的影响可能会导致癌症预防的新策略和规范轮班工作的新政策。
Epigenetic association studies have demonstrated differential promoter methylation in the core circadian genes in breast cancer cases relative to cancer-free controls. The current pilot study aims to investigate whether epigenetic changes affecting breast cancer risk could be caused by circadian disruption through exposure to light at night. Archived DNA samples extracted from whole blood of 117 female subjects from a prospective cohort conducted in Denmark were included in this study. A polymerase chain reaction (PCR)-based method was used for detection of gene-promoter methylation, whereas genome-wide methylation analysis was performed using the Illumina Infinium Methylation Chip. Long-term shiftwork resulted in the same promoter hypomethylation of CLOCK and hypermethylation of CRY2, as was previously observed in breast cancer case-control studies. Genome-wide methylation analysis further discovered widespread methylation alterations in shiftworkers, including changes in many methylation- and cancer-relevant genes. Pathway analysis of the genes with altered methylation patterns revealed several cancer-related pathways. One of the top three networks generated was designated as “DNA replication, recombination, and repair, gene expression, behavior” with ESR1 (estrogen receptor α) featured most prominently in the network, underscoring the potential breast cancer relevance of the genes differentially methylated in long-term shiftworkers. These results, although exploratory, demonstrate the first evidence of the cancer-relevant epigenetic effects of night shiftwork, which warrant further investigation. Considering there are millions of shiftworkers worldwide, understanding the effects of this exposure may lead to novel strategies for cancer prevention and new policies regulating shiftwork.
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DOI：
10.1158/1078-0432.ccr-08-2319
发表时间：
2009-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Suzuki J;Chen YY;Scott GK;Devries S;Chin K;Benz CC;Waldman FM;Hwang ES
通讯作者：
Hwang ES
影响因子：
51.1
作者：
Straif, Kurt;Baan, Robert;Cogliano, Vincent
通讯作者：
Cogliano, Vincent
影响因子：
3
作者：
Cavusoglu, A. Celebiler;Sevinc, A. I.;Sakizli, M.
通讯作者：
Sakizli, M.
影响因子：
2.8
作者：
Portaluppi, Francesco;Smolensky, Michael H.;Touitou, Yvan
通讯作者：
Touitou, Yvan
影响因子：
11.5
作者：
Parrella, P;Poeta, ML;Fazio, VM
通讯作者：
Fazio, VM