Blood metabolites as predictors of skin cancer risk: a comprehensive analysis

Abstract

Abstract Introduction This study aimed to investigate the potential causal effects of plasma metabolites on skin cancer (SC) risk through a two-sample Mendelian randomization (MR) analysis. Skin cancer, including melanoma and non-melanoma types, is a prevalent malignancy worldwide, necessitating the identification of novel biomarkers for early detection and prevention. Materials and Methods We utilized genome-wide association study (GWAS) data from 8,299 individuals of European ancestry in the Canadian Longitudinal Study of Aging (CLSA) cohort, encompassing 1,400 metabolites. The analysis also incorporated GWAS data from FinnGen, including 20,951 SC patients and 287,137 controls of European ancestry. The association between metabolites and SC risk was assessed using the inverse-variance weighted (IVW) method, complemented by sensitivity analyses such as MR-Egger and MR-PRESSO tests. Results The results revealed significant associations between 78 unique metabolites and SC risk. Among these, 42 metabolites were associated with a significant increase in SC risk, while 36 metabolites were linked to a significant reduction in SC risk. Conclusions This study highlights novel blood metabolites that are closely related to SC risk, emphasizing their potential importance in prioritizing metabolic features for SC mechanistic research. Further evaluation of these metabolites in SC risk assessment could lead to new insights into SC prevention and treatment strategies.