25-hydroxyvitamin D3 mediates the associations between urinary heavy metals and non- melanoma skin cancer: Insights from a population-based study

Background : The impact of combined heavy metal exposure on non-melanoma skin cancer (NMSC) in the general population remains poorly understood. Objective : To investigate the associations of metals with NMSC and examine the potential mediating effect of 25-hydroxyvitamin D3 [25(OH)D3]. Methods : We extracted data from the National Health and Nutrition Examination Survey, comprising 9835 participants with nine urinary metal concentrations, which were mercury (Hg), cesium (Cs), thallium (Tl), Ionium (Io), cobalt (Co), molybdenum (Mo), lead (Pb), barium (Ba), and arsenic (As). Multivariable logistic regression and weighted quantile sum regression were employed to estimate the associations of independent and combined metals with NMSC. Additionally, mediation analyses were conducted to explore the mediated effects of serum 25(OH)D3 on these associations. Results : Urinary levels of Hg, Io, Co, and mixed metals were positively correlated with NMSC. Serum 25(OH)D3 exhibited significant associations with NMSC, as did Hg, Cs, Tl, Io, Co, Mo, Pb, Ba, and combined metals with 25(OH)D3. Furthermore, the associations between single metals (primarily Hg and Io) and mixed metals with NMSC were partially mediated by 25(OH)D3. Limitations : Lack of validation in longitudinal study and independent populations. Conclusion : Metal exposure heightens NMSC risk, with a portion of this risk being mediated by 25(OH)D3.