Lifetime Ultraviolet Radiation Exposure and DNA Methylation in Blood Leukocytes: The Norwegian Women and Cancer Study

Christian M Page,Therese H Nøst,Arnoldo Frigessi,Magne Thoresen,Marit B Veierød,Reza Ghiasvand,Vera Djordjilović,Torkjel M Sandanger

doi:10.1038/s41598-020-61430-3

Abstract

Ultraviolet radiation (UVR) exposure is a leading cause of skin cancers and an ubiquitous environmental exposure. However, the molecular mechanisms relating UVR exposure to melanoma is not fully understood. We aimed to investigate if lifetime UVR exposure could be robustly associated to DNA methylation (DNAm). We assessed DNAm in whole blood in three data sets (n = 183, 191, and 125) from the Norwegian Woman and Cancer cohort, using Illumina platforms. We studied genome-wide DNAm, targeted analyses of CpG sites indicated in the literature, global methylation, and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. We used one data set for discovery and the other two for replication. One CpG site showed a genome-wide significant association to cumulative UVR exposure (cg01884057) (pnominal = 3.96e-08), but was not replicated in any of the two replication sets (pnominal ≥ 0.42). Two CpG sites (cg05860019, cg00033666) showed suggestive associations with the other UVR exposures. We performed extensive analyses of the association between long-term UVR exposure and DNAm. There was no indication of a robust effect of past UVR exposure on DNAm.

Highlights

Identification of biomarkers indicating past exposures is important in the study of chronic diseases and their etiology
Ultraviolet radiation (UVR) exposure is the main driver for skin photoaging, and we examined if lifetime UVR exposure could result in an accelerated epigenetic age, estimated from DNA methylation in leucocytes[19]
UVR exposures in the three sets are presented in Table 2, and R2 had lowest proportion of women from the region with highest ambient UVR

Summary

Introduction

Identification of biomarkers indicating past exposures is important in the study of chronic diseases and their etiology. UVR exposure has been linked to DNA methylation, as UVR exposure has been demonstrated to change the epigenetic profile of the epidermis[9]. An assessment of ambient UVR exposure and DNA methylation in CD4+ T-cells in European American individuals[10] demonstrated an epigenome-wide significant association for cg26930596 (PRKCZ), but failed to replicate in an independent sample. Our aim was to assess the former, i.e., whether DNA methylation in blood leucocytes is associated with life history of UVR exposure. We studied genome-wide DNA methylation as well as global www.nature.com/scientificreports methylation, including imputation of LINE-1 specific CpGs, in whole blood. UVR exposure is the main driver for skin photoaging, and we examined if lifetime UVR exposure could result in an accelerated epigenetic age, estimated from DNA methylation in leucocytes[19]. Analyses were performed in the discovery set and two replication sets

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Conclusion