Department of Public Health Sciences, Queen's University, Kingston, Canada.
Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Kingston, Canada.
Epigenetics. 2022 Oct;17(10):1259-1268. doi: 10.1080/15592294.2021.2009997. Epub 2021 Nov 26.
Night shift work is associated with increased breast cancer risk, but the molecular mechanisms are not well-understood. The objective of this study was to explore the relationship between night shift work parameters (current status, duration/years, and intensity) and methylation in circadian genes as a potential mechanism underlying the carcinogenic effects of night shift work. A cross-sectional study was conducted among 74 female healthcare employees (n = 38 day workers, n = 36 night shift workers). The Illumina Infinium MethylationEPIC beadchip was applied to DNA extracted from blood samples to measure methylation using a candidate gene approach at 1150 CpG loci across 22 circadian genes. Linear regression models were used to examine the association between night shift work parameters and continuous methylation measurements (β-values) for each CpG site. The false-discovery rate (q = 0.2) was used to account for multiple comparisons. Compared to day workers, current night shift workers demonstrated hypermethylation in the 5'UTR region of (q = 0.15). Individuals that worked night shifts for ≥10 years exhibited hypomethylation in the gene body of (q = 0.08) compared to those that worked <10 years. Hypermethylation in the gene body of was also apparent in those who worked ≥3 consecutive night shifts a week (q = 0.18). These findings suggest that night shift work is associated with differential methylation in core circadian genes, including and . Future, larger-scale studies with long-term follow-up and detailed night shift work assessment are needed to confirm and expand on these findings.
夜班工作与乳腺癌风险增加有关，但分子机制尚不清楚。本研究旨在探讨夜班工作参数（当前状态、持续时间/年和强度）与生物钟基因甲基化之间的关系，以期探索夜班工作致癌作用的潜在机制。本研究为一项横断面研究，共纳入 74 名女性医护人员（38 名白班工作者，36 名夜班工作者）。采用 Illumina Infinium MethylationEPIC beadchip 对血液样本中的 DNA 进行检测，采用候选基因方法在 22 个生物钟基因中的 1150 个 CpG 位点上进行 1150 个 CpG 位点的甲基化测量。采用线性回归模型，检验夜班工作参数与每个 CpG 位点连续甲基化测量值（β 值）之间的关系。采用错误发现率（q=0.2）校正多重比较。与白班工作者相比，当前夜班工作者在 5'UTR 区域的 表现出超甲基化（q=0.15）。与工作年限<10 年的人群相比，工作年限≥10 年的人群在 基因体中表现出低甲基化（q=0.08）。每周至少连续上 3 个夜班的人群在 基因体中也表现出高甲基化（q=0.18）。这些发现表明，夜班工作与核心生物钟基因（包括 和 ）的差异甲基化有关。未来需要更大规模、长期随访和详细夜班工作评估的研究来证实和扩展这些发现。
