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

Publication date: Jul 01, 2025

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.

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Concepts Keywords
Cancer Carcinoma, Basal Cell
Cutaneous Carcinoma, Squamous Cell
Genome Genetic correlation
Raps Genome-Wide Association Study
Statistics Humans
Keratosis, Actinic
Melanoma
Mendelian randomization
Mendelian Randomization Analysis
Microbiota
Polymorphism, Single Nucleotide
Skin
Skin cancer
Skin Microbiome
Skin microbiome
Skin Neoplasms

Semantics

Type Source Name
disease MESH skin cancers
disease MESH basal cell carcinoma
pathway KEGG Basal cell carcinoma
disease MESH squamous cell carcinoma
disease MESH melanoma
pathway KEGG Melanoma
disease MESH actinic keratosis
disease MESH causality
disease MESH carcinoma
disease MESH morbidity
disease MESH tumor
pathway REACTOME Immune System
disease MESH physical barrier
disease MESH Skin Diseases
disease MESH Infection
drug DRUGBANK Coenzyme M
disease MESH psoriasis
disease MESH atopic dermatitis
disease MESH acne
disease MESH dysbiosis
disease MESH carcinogenesis
disease MESH scars

Original Article

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