Ritonja Jennifer A, Aronson Kristan J, Leung Michael, Flaten Lisa, Topouza Danai G, Duan Qing Ling, Durocher Francine, Tranmer Joan E, Bhatti Parveen
Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada
Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
Occup Environ Med. 2022 May 2. doi: 10.1136/oemed-2021-108111.
Mechanisms underlying the carcinogenicity of night shift work remain uncertain. One compelling yet understudied cancer mechanism may involve altered DNA methylation in circadian genes due to melatonin secretion patterns. The objective of this study was to explore the relationship between melatonin secretion patterns and circadian gene methylation among day and night shift workers.
Female healthcare employees (n=38 day workers, n=36 night shift workers) for whom we had urinary 6-sulfatoxymelatonin secretion data from a previous study were recontacted. New blood samples were collected and used to measure methylation levels at 1150 CpG loci across 22 circadian genes using the Illumina Infinium MethylationEPIC beadchip. Linear regression was used to examine the association between melatonin (acrophase and mesor) and M values for each CpG site (false discovery rate, q=0.2), while testing for effect modification by shift work status.
Among night shift workers, a higher mesor (24 hours of mean production of melatonin) was associated with increased methylation in the body of (q=0.02) and decreased methylation in the putative promoter region of (q=0.03). Later acrophase (ie, time of peak concentration) was associated with increased methylation in the putative promoter region of (q=0.20) and decreased methylation in the body of (q=0.20). No associations were identified among day workers.
In conclusion, patterns in melatonin secretion were associated with differential circadian gene methylation among night shift workers. Melatonin and alteration of DNA methylation in circadian genes may be one pathway towards increased cancer risk, although larger-scale studies examining multiple time points are needed.
夜班工作致癌的潜在机制尚不清楚。一个引人关注但研究不足的癌症机制可能涉及由于褪黑素分泌模式导致的昼夜节律基因DNA甲基化改变。本研究的目的是探讨日班和夜班工作者中褪黑素分泌模式与昼夜节律基因甲基化之间的关系。
重新联系了我们之前一项研究中有尿6-硫酸氧褪黑素分泌数据的女性医护人员（n = 38名日班工作者，n = 36名夜班工作者）。采集新的血液样本，并使用Illumina Infinium MethylationEPIC芯片测定22个昼夜节律基因中1150个CpG位点的甲基化水平。使用线性回归检验每个CpG位点的褪黑素（峰相位和中值）与M值之间的关联（错误发现率，q = 0.2），同时检验轮班工作状态的效应修饰。
在夜班工作者中，较高的中值（24小时褪黑素平均分泌量）与[具体基因1]基因主体甲基化增加（q = 0.02）和[具体基因2]假定启动子区域甲基化减少（q = 0.03）相关。较晚的峰相位（即浓度峰值时间）与[具体基因3]假定启动子区域甲基化增加（q = 0.20）和[具体基因4]基因主体甲基化减少（q = 0.20）相关。在日班工作者中未发现关联。
总之，褪黑素分泌模式与夜班工作者中昼夜节律基因甲基化差异有关。褪黑素和昼夜节律基因DNA甲基化改变可能是癌症风险增加的一条途径，尽管需要更大规模的研究来检查多个时间点。
