Nightshift Work and DNA Methylation of Circadian Genes

项目摘要 据估计，北美和欧洲有15%到20%的工人从事夜班工作， 夜间工作可能会增加患癌症的风险，这是一个重要的公众关注 健康问题。考虑到实验证据和流行病学证据之间的差异 夜班工作的致癌性，对夜班工人影响的生物标记物的研究可以提供 关于可能的病因学联系的重要新信息。核心昼夜节律基因对于 昼夜节律的调节和这些基因参与了许多重要的机制 致癌。因此，通过DNA甲基化的调节，这些基因的差异表达可能是 夜班工人患癌症风险增加的一种机制。总体目标 这项可行性研究的目的是确定在昼夜节律中是否可以检测到差异甲基化位点 利用来自仔细评估的一组轮班工人的现有样本，研究夜班和白班工人之间的基因 工人们。这将是第一项能够评估男性和女性这种差异的研究。 中心假设是，与夜班工作相关的昼夜节律紊乱会导致差异 昼夜节律基因的表达，通过这些基因中基因座的差异甲基化表现出来。在……里面 此外，还将评估适应夜班工作的措施，如时型和睡眠质量 对夜班工人DNA甲基化的潜在影响。利用现有的血液样本 问卷数据，这项研究建议评估那些在抽血时活跃的受试者 上夜班1年(n=230)和积极上白班工作1年(n=230) 114例。这些假设将通过追求以下具体目标来检验：1)评估在 12个核心昼夜节律基因中334个基因的甲基化发生在夜班和白班工人之间；2) 探索性分析，评估性别、种族、时型和睡眠质量是否影响夜班工作 334个基因座的DNA甲基化。这项研究将为追求大的 倒班工人中表观遗传和其他生物标志物的规模调查。此外，这一结果 这项研究将有助于通过提供数据来设计未来检查癌症风险的流行病学研究 关于收集最相关的工作历史和与睡眠有关的数据，纳入 潜在有用的生物标志物和新假说的产生。预计这一研究方向 最终将为干预措施提供目标，以减轻夜班工人的负面健康影响。

Project Summary With an estimated 15 to 20% of workers in North America and Europe engaged in nightshift work, the possibility that working at night can result in an increased risk of developing cancer is an important public health concern. Given the discrepancy between the strength of experimental and epidemiologic evidence for the carcinogenicity of nightshift work, studies of biomarkers of effect among nightshift workers can provide important new information regarding the possible etiologic link. The core circadian genes are essential for regulation of circadian rhythms and these genes are involved in a number of mechanisms important to carcinogenesis. Thus, differential expression of these genes, through modulation of DNA methylation, may be a mechanism by which nightshift workers are at an increased risk of developing cancer. The overall objective of this feasibility study is to determine whether differentially methylated sites can be detected in circadian genes between night and dayshift workers using existing samples from a carefully evaluated group of shift workers. This will be the first study with the capability to evaluate such differences in both men and women. The central hypothesis is that circadian disruption associated with working the nightshift results in differential expression of circadian genes that is manifest through differential methylation of loci in these genes. In addition, measures of adaptability to nightshift work, such as chronotype and sleep quality, will be evaluated for a potential impact on DNA methylation among nightshift workers. Using existing blood samples and questionnaire data, the study proposes to evaluate subjects who, at the time of blood draw, were actively working the nightshift for e1 year (n=230) and subjects who were actively working the dayshift for e1 year (n=114). The hypotheses will be tested by pursuing the following specific aims: 1) Evaluate differences in methylation at 334 loci in the 12 core circadian genes between established night and dayshift workers; 2) In exploratory analyses, evaluate if gender, race, chronotype and sleep quality affect the impact of nightshift work on DNA methylation at the 334 loci. This study will provide essential preliminary data for the pursuit of large scale investigations of epigenetic and other biomarkers among shift workers. Furthermore, the results of this study will be useful to the design of future epidemiologic studies examining cancer risk by providing data regarding the collection of the most relevant work history and sleep-related data, the incorporation of potentially useful biomarkers and the generation of new hypotheses. It is anticipated that this line of research will ultimately provide targets for interventions to mitigate negative health effects among nightshift workers.