Investigating the relationship between melatonin patterns and methylation in circadian genes among day shift and night shift workers

Abstract

ObjectivesMechanisms 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.MethodsFemale 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.ResultsAmong 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.ConclusionsIn 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.

Photoperiod Induces DNA Methylation Changes in the Melatonin Receptor 1A Gene in Ewes

“…Although the MTNR1A gene is thought to be related to ovine estrus or reproduction, it has not been studied from the perspective of DNA methylation in the promoter region. One previous study reported that the alteration of DNA methylation in the putative promoter region of the MTNR1A gene may induce pathways that increase cancer risk for nightshift workers [ 40 ]. In our present study, using a luciferase reporter gene, we constructed vectors carrying different lengths of the MTNR1A gene promoter sequence and identified the core promoter region to be in the 540 bp region upstream of the TSS ( Figure 2 ).…”

Homo sapiens May Incorporate Daily Acute Cycles of “Conditioning–Deconditioning” to Maintain Musculoskeletal Integrity: Need to Integrate with Biological Clocks and Circadian Rhythm Mediators

“…Evaluation of systemic mediators (i.e., myokines and osteokines) in serum from those working during the day vs. night could be evaluated to gain insights into interactions with circadian rhythm mediators regarding levels. Evidence for this concept has been reported by James et al [ 166 ] and Ritonja et al [ 167 ], indicating that shift work can lead to alterations in circadian rhythm mediator expression as well as epigenetic alteration to relevant genes. For others, it may even be possible to perform such studies using individuals who work alternating shift work, and thus potentially addressing individual variation in responsiveness.…”

Melatonin: A Potential Regulator of DNA Methylation

“…The latest research has highlighted that changes in melatonin synthesis and the circadian rhythm are related to cancer development [ 110 , 111 , 112 ]. There is a relationship between disturbances in the circadian rhythm and genomic instability [ 113 , 114 ].…”

“…The studies involving night shift workers indicated that melatonin secretion is associated with distinctive methylation pattern of genes implicated in the circadian cycle [ 112 , 121 ]. A cross-sectional study, including nurses and midwives who worked day shifts and rotating night shifts, showed differential blood-based DNA methylation statuses in the circadian genes in the latter group [ 121 ].…”