Risk–benefit balance of habitual ultraviolet exposure for cardiovascular, cancer, and skin cancer mortality: UK Biobank cohort study

Abstract

Objective To 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. Design A population-based prospective cohort study with epidemiological and proteomic mediation analyses. Setting UK Biobank, recruited from 22 assessment centres across England, Scotland, and Wales. Participants 419 007 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 measures Habitual 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. Results Compared 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. Conclusions Higher 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.

AI evidence extraction

Main findings

Compared with low habitual UV exposure (Sun-BEEM), medium and high exposure were associated with lower all-cause mortality (HR 0.89 and 0.84, respectively) and showed similar inverse associations for cardiovascular and non-skin cancer mortality. Skin cancer mortality showed no clear dose–response with UV exposure, while incident keratinocyte cancers increased across exposure categories; counterfactual modelling suggested potential net prevention of cardiovascular and other cancer deaths relative to additional melanoma/keratinocyte cancer deaths if associations are causal.

Outcomes measured

• All-cause mortality
• Cardiovascular mortality
• Cancer mortality (non-skin)
• Skin cancer mortality
• Incident cardiovascular disease
• Incident cancer
• Incident keratinocyte cancers
• Melanoma deaths (counterfactual modelling mentioned)

{
    "study_type": "cohort",
    "exposure": {
        "band": null,
        "source": "sunlight (ultraviolet exposure)",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Adults of White European ancestry in UK Biobank (England, Scotland, Wales)",
    "sample_size": 419007,
    "outcomes": [
        "All-cause mortality",
        "Cardiovascular mortality",
        "Cancer mortality (non-skin)",
        "Skin cancer mortality",
        "Incident cardiovascular disease",
        "Incident cancer",
        "Incident keratinocyte cancers",
        "Melanoma deaths (counterfactual modelling mentioned)"
    ],
    "main_findings": "Compared with low habitual UV exposure (Sun-BEEM), medium and high exposure were associated with lower all-cause mortality (HR 0.89 and 0.84, respectively) and showed similar inverse associations for cardiovascular and non-skin cancer mortality. Skin cancer mortality showed no clear dose–response with UV exposure, while incident keratinocyte cancers increased across exposure categories; counterfactual modelling suggested potential net prevention of cardiovascular and other cancer deaths relative to additional melanoma/keratinocyte cancer deaths if associations are causal.",
    "effect_direction": "mixed",
    "limitations": [],
    "evidence_strength": "moderate",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "no",
    "keywords": [
        "ultraviolet",
        "sunlight",
        "habitual exposure",
        "Sun-BEEM",
        "UK Biobank",
        "prospective cohort",
        "mortality",
        "cardiovascular disease",
        "cancer",
        "skin cancer",
        "keratinocyte cancer",
        "proteomics",
        "mediation analysis",
        "g-computation"
    ],
    "suggested_hubs": []
}

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