Department of Pediatrics/U.S. Department of Agriculture/Agricultural Research Service/ Children's Nutrition Research Center, Baylor College of Medicine , Houston, TX , USA.
Ann Med. 2014 Jun;46(4):208-20. doi: 10.3109/07853890.2014.914808. Epub 2014 Jun 5.
Humans as diurnal beings are active during the day and rest at night. This daily oscillation of behavior and physiology is driven by an endogenous circadian clock not environmental cues. In modern societies, changes in lifestyle have led to a frequent disruption of the endogenous circadian homeostasis leading to increased risk of various diseases including cancer. The clock is operated by the feedback loops of circadian genes and controls daily physiology by coupling cell proliferation and metabolism, DNA damage repair, and apoptosis in peripheral tissues with physical activity, energy homeostasis, immune and neuroendocrine functions at the organismal level. Recent studies have revealed that defects in circadian genes due to targeted gene ablation in animal models or single nucleotide polymorphism, deletion, deregulation and/or epigenetic silencing in humans are closely associated with increased risk of cancer. In addition, disruption of circadian rhythm can disrupt the molecular clock in peripheral tissues in the absence of circadian gene mutations. Circadian disruption has recently been recognized as an independent cancer risk factor. Further study of the mechanism of clock-controlled tumor suppression will have a significant impact on human health by improving the efficiencies of cancer prevention and treatment.
人类作为昼行性动物，在白天活动，晚上休息。这种行为和生理的日常波动是由内在的生物钟驱动的，而不是环境线索。在现代社会，生活方式的改变导致内在的生物钟稳态经常被打乱，从而增加了患各种疾病（包括癌症）的风险。生物钟由生物钟基因的反馈回路控制，通过将细胞增殖和代谢、DNA 损伤修复和细胞凋亡与身体活动、能量稳态、免疫和神经内分泌功能在机体水平上耦合，来控制日常生理。最近的研究表明，由于动物模型中靶向基因缺失或人类中单核苷酸多态性、缺失、失调和/或表观遗传沉默导致的生物钟基因缺陷与癌症风险增加密切相关。此外，即使没有生物钟基因突变，昼夜节律的破坏也会破坏外周组织中的分子钟。昼夜节律破坏最近被认为是一个独立的癌症风险因素。对时钟控制肿瘤抑制机制的进一步研究将通过提高癌症预防和治疗的效率，对人类健康产生重大影响。
