He Yong, Li Liming, Li Yuancheng, Wang Xiaoke, Qian Leqi, Yang Jiajia, Jiang Mingjun
Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, China.
Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China.
Sci Rep. 2025 Jul 1;15(1):21590. 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.
越来越多的证据表明皮肤微生物群与不同类型的皮肤癌之间存在联系,但这种联系是否具有因果关系仍不确定。本研究旨在调查基因预测的皮肤微生物群与皮肤癌之间的因果关系,包括基底细胞癌(BCC)、皮肤鳞状细胞癌(CSCC)、皮肤黑色素瘤(CM)和光化性角化病(AK)。使用公开的全基因组关联研究(GWAS)统计汇总数据集进行了两样本孟德尔随机化(MR)分析。应用了多种方法,包括逆方差加权(IVW)、MR-Egger、加权中位数、加权模式和稳健调整轮廓评分(RAPS)。进行了敏感性分析以评估结果的稳健性,并进行了反向MR分析以评估潜在的反向因果关系。总共选择了1224个单核苷酸多态性(SNP)作为78种属水平皮肤微生物的工具变量(IV)。六种属水平的皮肤微生物与皮肤癌表现出提示性关联。敏感性和水平多效性分析证实了这些关系的稳健性。反向MR分析显示,在已鉴定的皮肤微生物群分类群与皮肤癌之间没有反向因果关系的证据。本研究确定了皮肤微生物群与四种皮肤癌之间的潜在因果关系。需要进一步的研究来证实这些结果并阐明潜在机制。
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