Mendelian randomization study reveals causal association between skin microbiome and skin cancers

• Published in: Scientific reports Vol. 15; no. 1; pp. 21590 - 9
• Main Authors: He, Yong, Li, Liming, Li, Yuancheng, Wang, Xiaoke, Qian, Leqi, Yang, Jiajia, Jiang, Mingjun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2025; Nature Portfolio
• Subjects: 631/326; 631/67; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - microbiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - microbiology; Genetic correlation; Genome-Wide Association Study; Humanities and Social Sciences; Humans; Keratosis, Actinic - genetics; Keratosis, Actinic - microbiology; Melanoma - genetics; Melanoma - microbiology; Mendelian randomization; Mendelian Randomization Analysis; Microbiota - genetics; multidisciplinary; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Skin - microbiology; Skin cancer; Skin Microbiome; Skin Neoplasms - genetics; Skin Neoplasms - microbiology; Genetic correlation; Mendelian randomization; Skin microbiome; Skin cancer
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-07265-2

Increasing evidence indicates a link between the skin microbiome and different types of skin cancer, but it is still uncertain if this connection is causal. This study aimed to investigate the causal relationship between genetically predicted skin microbiome and skin cancer, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), cutaneous melanoma (CM), and actinic keratosis (AK). A two-sample Mendelian randomization (MR) analysis was conducted using summary datasets of public genome-wide association study (GWAS) statistics. Multiple methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and robust adjusted profile score (RAPS), were applied. Sensitivity analyses were performed to assess the robustness of the results, and a reverse MR analysis was conducted to evaluate potential reverse causality. A total of 1224 SNPs were selected as instrumental variables (IVs) for 78 genus-level skin microbes. Six genus-level skin microbes exhibited suggestive associations with skin cancer. Sensitivity and horizontal pleiotropy analyses confirmed the robustness of these relationships. Reverse MR analysis showed no evidence of reverse causality between the identified skin microbiota taxa and skin cancers. This study identifies potential causal relationships between skin microbiota and four skin cancers. Additional studies are needed to confirm these results and elucidate the underlying mechanisms.