Lewis Philip, Hellmich Martin, Fritschi Lin, Tikellis Gabriella, Morfeld Peter, Groß J Valérie, Foster Russell G, Paltiel Ora, Klebanoff Mark A, Golding Jean, Olsen Sjurdur, Magnus Per, Ponsonby Anne-Louise, Linet Martha S, Ward Mary H, Caporaso Neil, Dwyer Terence, Erren Thomas C
Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne , Cologne, Germany.
Institute for Medical Statistics and Computational Biology (IMSB), Faculty of Medicine & University Hospital of Cologne , Cologne, Germany.
Chronobiol Int. 2020 Jul;37(7):1034-1047. doi: 10.1080/07420528.2020.1740724. Epub 2020 Apr 1.
Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose-responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0-24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8-16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84-0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse ["protective"] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8-16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.
实验证据表明，围产期生物钟和系统的光印记可能会影响后期生活中的下游生理学和癌症风险。对于人类来说，主要的昼夜节律刺激是每日的明暗循环。在此，我们探讨围产期光周期特征（光周期：由一年中的时间和地点决定的白昼时长）与儿童癌症风险之间的关联。我们使用了国际儿童癌症队列联盟（I4C）中六个国家（澳大利亚、丹麦、以色列、挪威、英国、美国）前瞻性出生队列中182,856名母亲和婴儿的汇总数据。采用Cox比例风险回归来估计风险比（HRs）和95%置信区间（CIs）。与预测的剂量反应差异一致，受限立方样条表明围产期平均每日光周期（0 - 24小时）与儿童癌症风险之间存在潜在的非线性、非单调关系。在对154,121名仅在8 - 16小时范围内经历孕晚期光周期的个体进行的受限分析中，孕晚期平均每日光周期每增加一小时，患儿童癌症的相对风险降低9%[HR：0.91（95%CI：0.84 - 0.99）]。总之，在这项关于围产期光周期与儿童癌症的首次研究中，我们在总研究人群8 - 16小时范围内检测到孕晚期平均每日光周期与儿童癌症风险之间存在反向["保护"]线性关联。有限的统计效力阻碍了对暴露于更极端光周期个体风险的调查。未来需要开展研究来确认与光周期相关的不同风险，并对假设的昼夜节律印记机制进行进一步调查是必要的。
