Association Between Serum Uric Acid Levels and Skin Cancer: Results from NHANES Data and Mendelian Randomization Analysis

Yihao Niu,1 Shengming Shi,1 Yongxia Chen,1 Shuangyuan Yang,1 Peiyu Yan,1,2,* Jiyou Kou3,* 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, Macau SAR, People’s Republic of China; 3Department of Preventive Medicine, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peiyu Yan, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, People’s Republic of China, Email [email protected] Jiyou Kou, Department of Preventive Medicine, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai, Guangdong Province, People’s Republic of China, Email [email protected]: Previous studies have suggested that serum uric acid (SUA), a byproduct of purine metabolism, may be associated with cancer development. However, the relationship between SUA levels and skin cancers—malignant melanoma (MM) and non-melanoma skin cancer (NMSC)—remains poorly understood. The main purpose of this study is to investigate the relationship between serum uric acid levels and the risk of malignant melanoma and non-melanoma skin cancer.Patients and Methods: This research examined NHANES data (1999– 2020) to explore the association between serum uric acid levels and skin cancer risk in a cohort of 1219 patients (336 mm cases and 883 NMSC cases). Using Mendelian randomization (IVW as primary method, MR-Egger and weighted median as secondary approaches), GWAS data evaluated causality. Sensitivity tests were conducted to ensure the robustness of the findings, while RCS models were used to analyze nonlinear exposure-outcome relationships. Multivariable regression models were employed to adjust for age, sex, race, lifestyle, and comorbidities, thereby isolating the independent effect of serum uric acid.Results: High serum uric acid (SUA) levels are strongly linked to increased risks of MM and NMSC, particularly in women and Mexican American populations. Risk trends vary at different SUA thresholds, and elevated levels are tied to other negative health outcomes. However, no causal relationship between SUA levels and skin cancer has been established.Conclusion: This study addresses gaps in prior research by revealing a significant association between high serum uric acid (SUA) levels and increased risks of both malignant melanoma (MM) and non-melanoma skin cancer (NMSC). Notably, SUA may serve as a valuable biomarker for risk assessment, particularly among women and Mexican Americans. Even so, further research is needed to better understand the biological mechanisms underlying SUA’s role in skin cancer development.Keywords: observational studies, risk factor, cancer, NHANES, Mendelian randomization analysis