Skin cancer, the most common global malignancy, is linked to ultraviolet (UV)-driven serum 25-hydroxyvitamin D (25(OH)D)synthesis, with its controversial role possibly reflecting cumulative UV exposure. This study aimed to assess the association and causality between 25(OH)D levels and skin cancer risk using the National Health and Nutrition Examination Survey (1999–2018) data and Mendelian randomization (MR) analyses, evaluating 25(OH)D as a screening biomarker.
Methods
We integrated data from the National Health and Nutrition Examination Survey (1999–2018; n = 21,357 U.S. adults, including 631 skin cancer cases) with MR analyses using genome-wide association study-derived genetic variants to assess the causal relationship between serum 25(OH)D levels and skin cancer risk.
Results
Higher 25(OH)D levels were associated with increased risks of nonmelanoma skin cancer [odds ratio (OR) (95% confidence interval (CI)) = 2.94 (2.10, 4.20)], melanoma [OR (95% CI) = 2.94 (1.73, 5.28)], and other skin cancers [OR (95% CI) = 2.10 (1.36, 3.36)]. MR analyses supported a causal relationship for nonmelanoma skin cancer [OR (95% CI) = 1.01 (1.00, 1.02)] and melanoma [OR (95% CI) = 1.00 (1.00, 1.01)]. Risks were highest in males, older adults, and individuals with obesity.
Conclusions
Higher serum 25(OH)D levels are associated with increased skin cancer risk, likely reflecting cumulative UV exposure. Routine monitoring of 25(OH)D, combined with UV exposure management, is recommended for risk stratification in skin cancer screening, particularly among high-risk groups. Validation in multiethnic cohorts is needed to confirm these findings.
Full text
https://www.xiahepublishing.com/2835-3315/CSP-2025-00010
The study was recently published in the Cancer Screening and Prevention .
Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.
