Risk-Benefit Balance of Habitual Ultraviolet Exposure for Cardiovascular, Cancer, and Skin Cancer Mortality: A UK Biobank Cohort Study

ObjectiveTo examine how habitual ultraviolet (UV) exposure relates to cause-specific mortality and incidence, to quantify trade-offs between non-skin disease and skin cancer, and to explore potential circulating mediators. DesignA population-based prospective cohort study with epidemiological and proteomic mediation analyses. SettingUK Biobank, recruited from 22 assessment centres across England, Scotland, and Wales. Participants419 007 adults of White European ancestry with data on habitual UV exposure and follow-up for mortality and incident cardiovascular disease and cancer. A proteomic subcohort of 44 712 participants had plasma profiling. Main outcome measuresHabitual ultraviolet exposure was summarised using Sun-BEEM (Sun-Behavioural and Environmental Exposure Model), a multidimensional score integrating environmental and behavioural indicators, categorised as low, medium, or high. Primary outcomes were all-cause, cardiovascular, and cancer mortality and incidence, and associations with Sun-BEEM categories were estimated using multivariable Cox models. Two extensions were implemented: an epidemiological extension using parametric g-computation to estimate deaths under counterfactual low and high UV scenarios; and a biological extension using proteomic mediation analyses to identify circulating proteins potentially linking UV exposure to cardiovascular and cancer mortality. ResultsCompared with low Sun-BEEM, medium and high exposure were associated with lower all-cause mortality (hazard ratio 0.89, 95% confidence interval 0.87 to 0.91; and 0.84, 0.82 to 0.87), with similar inverse associations for cardiovascular and non-skin cancer mortality. Skin cancer mortality showed no clear dose-response relationship with UV exposure, although incident keratinocyte cancers increased across Sun-BEEM categories. Counterfactual modelling suggested that, if associations are causal, a uniformly high UV pattern would prevent many more cardiovascular and other cancer deaths than the additional melanoma and keratinocyte cancer deaths. Proteomic mediation analyses implicated UV-downregulated immunoregulatory, mucosal-barrier, and cardiorenal-neuroendocrine pathways. ConclusionsHigher habitual UV exposure, measured using a multidimensional score, was associated with lower cardiovascular and non-skin cancer mortality without clear increases in skin cancer mortality, supporting a more balanced view of sunlight and health. Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPublic health advice in temperate countries mainly treats sunlight as a skin cancer hazard. C_LIO_LIFew studies have explicitly quantified the trade-off between the potential benefits of habitual ultraviolet exposure for major non-skin diseases and its harms for skin cancer. C_LIO_LIMechanistic research on how ultraviolet exposure affects health outcomes has focused largely on vitamin D, with only limited work on non-vitamin D pathways. C_LI What this study addsO_LIA multidimensional UV exposure score (Sun-BEEM), combining environmental and behavioural indicators, was associated with lower all-cause, cardiovascular, and non-skin cancer mortality, without clear increases in skin cancer mortality. C_LIO_LICounterfactual analyses suggested a net balance favouring cardiovascular and cancer mortality benefits over skin cancer harms; proteomics supported mainly non-vitamin D pathways. C_LI