Objectives Mechanisms underlying the carcinogenicity of night shift work remain uncertain. One compelling yet understudied cancer mechanism may involve altered DNA methylation in circadian genes due to melatonin secretion patterns. The objective of this study was to explore the relationship between melatonin secretion patterns and circadian gene methylation among day and night shift workers.
Methods Female healthcare employees (n=38 day workers, n=36 night shift workers) for whom we had urinary 6-sulfatoxymelatonin secretion data from a previous study were recontacted. New blood samples were collected and used to measure methylation levels at 1150 CpG loci across 22 circadian genes using the Illumina Infinium MethylationEPIC beadchip. Linear regression was used to examine the association between melatonin (acrophase and mesor) and M values for each CpG site (false discovery rate, q=0.2), while testing for effect modification by shift work status.
Results Among night shift workers, a higher mesor (24 hours of mean production of melatonin) was associated with increased methylation in the body of RORA (q=0.02) and decreased methylation in the putative promoter region of MTNR1A (q=0.03). Later acrophase (ie, time of peak concentration) was associated with increased methylation in the putative promoter region of MTNR1A (q=0.20) and decreased methylation in the body of PER3 (q=0.20). No associations were identified among day workers.
Conclusions In conclusion, patterns in melatonin secretion were associated with differential circadian gene methylation among night shift workers. Melatonin and alteration of DNA methylation in circadian genes may be one pathway towards increased cancer risk, although larger-scale studies examining multiple time points are needed.
- Shift Work Schedule
- Circadian Rhythm
Data availability statement
Deidentified participant data that support the findings of this study are available from the corresponding author, JAR, upon reasonable request. For more information, please email firstname.lastname@example.org.
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Contributors The study described in this manuscript was designed and conducted by JAR, KJA, JET and FD. Bioinformatics for the DNA methylation data was conducted by LF, DGT and QLD. Project conceptualisation for this paper, statistical analysis, interpretation of results and manuscript writing was performed by JAR with supervision from PB, KJA and JET, and with additional feedback and guidance from ML, LF, DGT, QLD and FD. JAR is the guarantor of this manuscript, and accepts full responsibility for the finished work, conduct and publication of the study.
Funding This study was funded by the Cancer Research Society (Montreal), under Cancer Research Society/Environment Cancer Fund – Read for the Cure Operating Grant (number 23218), the Canadian Institutes of Health Research (number 111023), the Workplace Safety and Insurance Board (Ontario) (number 07005) and the Queen’s University Faculty of Health Sciences Garfield Kelly Cardiovascular Research & Development Fund (number 6026402).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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