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

Background 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 influences DNA methylation, and if individual CpG sites could be robustly associated with UVR exposures.Methods We assessed DNA methylation in whole blood in three data sets (N = 183, 191, and 125) from the Norwegian Women and Cancer cohort, using Illumina methylation platforms (450k & EPIC). We studied genome-wide DNA methylation, targeted analyses of CpG sites indicated in the literature, global methylation (average over all CpGs and imputation of LINE-1 specific CpGs), and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. Cumulative UVR exposure was calculated by adding sunbathing vacations and indoor tanning. We used one data set for discovery and the other two for replication. Results One CpG site showed a genome-wide significant association between cumulative UVR exposure and DNA methylation (cg01884057) (pnominal=3.96e-08), but was not replicated in any of the two replication sets (pnominal≥0.42). Four CpG sites (cg05860019, cg00033666, cg18984282, cg25792367) showed suggestive associations with the other UVR exposures. Conclusion We performed extensive analyses of the association between long-term UVR exposure and DNA methylation in lymphocytes. There was no indication of a robust effect of past UVR exposure on DNA methylation, and our results do not suggest mediation of UVR effects on melanoma risk by DNA methylation.