Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

中文翻译：

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夜班时间表导致 DNA 修复基因的昼夜节律失调和人类 DNA 损伤增加

昼夜节律紊乱已被确定为肥胖、心血管疾病和癌症等健康疾病的危险因素。尽管流行病学研究表明，由于夜班工作，与昼夜节律失调相关的各种癌症的风险增加，但其潜在机制尚未阐明。我们试图研究癌症标志途径基因的昼夜节律破坏可能在轮班工人癌症风险增加中发挥的潜在机制作用。在一项受控实验室研究中，我们在模拟白班或夜班 3 天后的 24 小时恒定常规方案中，研究了从健康年轻人获得的循环白细胞中癌症标志通路基因和相关生物通路的昼夜节律转录组。模拟的夜班时间表显着改变了参与癌症标志性途径的基因的正常昼夜节律。DNA 修复途径显示在模拟白班时间表后节律基因显着富集，但不遵循模拟夜班时间表。在功能评估中，我们证明暴露于模拟夜班后，对内源性和外源性 DNA 损伤源的敏感性增加。我们的研究结果表明，DNA 修复的昼夜节律失调可能会增加 DNA 损伤并增加夜班工人的癌症风险。但不遵循模拟的夜班时间表。在功能评估中，我们证明暴露于模拟夜班后，对内源性和外源性 DNA 损伤源的敏感性增加。我们的研究结果表明，DNA 修复的昼夜节律失调可能会增加 DNA 损伤并增加夜班工人的癌症风险。但不遵循模拟的夜班时间表。在功能评估中，我们证明暴露于模拟夜班后，对内源性和外源性 DNA 损伤源的敏感性增加。我们的研究结果表明，DNA 修复的昼夜节律失调可能会增加 DNA 损伤并增加夜班工人的癌症风险。