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Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and non-cutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined three U.S. prospective cohorts, the Health Professionals Follow-Up Study (HPFS) (1986) and Nurses’ Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding non-melanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 males; 212,449 females) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as reference for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared to the lowest quintile, risk of any cancer was slightly increased across all other quintiles [highest quintile Hazard Ratio (HR),1.04; 95% Confidence Interval (CI),1.01,1.07; P-heterogeneity (P-het)=0.41]. All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR,1.17; 95% CI,1.04,1.31; P-het=0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and non-cutaneous cancers.

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