Perinatal photoperiod and childhood cancer: pooled results from 182,856 individuals in the international childhood cancer cohort consortium (I4C)

ABSTRACT

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.

KEYWORDS:

• Perinatal
• light
• circadian
• childhood cancer
• leukemia
• cohort
• PLICCS

Acknowledgments

We are extremely grateful to all the families who took part in the respective cohorts, medical personnel, and the individuals involved in recruitment, data collection, organization, and upkeep of the respective cohorts and the I4C consortium. We also thank Dr. Frank Steffany (University of Cologne) for lending expert meteorological expertise at the beginning of this project.

Author Contributions

TE conceived the hypothesis (2011) and organized the project thereafter. PL, TE, and JVG designed the study. PL, MH, LF, and PM conducted analyses. PL, MH, LF, PM, and TE interpreted results. PL and TE wrote the manuscript draft. LF and ALP contributed to the epidemiological aspects of the discussion. RF contributed to the light-associated aspects of the discussion. I4C representatives contributed data for the analyses. All authors commented on the manuscript draft, approved the submission, and are accountable for the work. TE and PL contributed equally to this study.

Disclosure of Interest

All authors declare no conflict of interest.

Data Availability

Please contact Gabriella Tikellis at the Murdoch Childrens Research Institute (Australia) regarding the availability of the International Childhood Cancer Cohort Consortium (I4C) data. E: [email protected]

Supplementary Material

The supplementary data for this article can be accessed on the publisher’s website.

Additional information

Funding

The NIH intramural research program (NCI, NICHD) – USA; National Children’s Study – USA; Tour de Cure – Australia; the Children’s Cancer Centre Foundation - Australia; Bluey Day Foundation – Australia; Baxter Family Foundation – Australia; The Rotary Club of North Brighton – Australia; Private philanthropic donations – Australia; and Murdoch Children’s Research Institution [M1300049], Australia. The UK Medical Research Council and the Wellcome Trust [Grant ref: 092731] and the University of Bristol currently provide core support for ALSPAC. The Maria Ascoli Foundation, Jerusalem, Israel, provided support for data pooling of the JPS.