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

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.