Causal association between oral microbiota and oral cancer: a mendelian randomization study

Abstract Many studies have reported an association between oral microbiota and oral cancer (OC). Yet, the causal relationship between oral microbiota and OC remains undetermined. This Mendelian randomization (MR) study utilized the most recent genome-wide association study of oral microbiota from th...

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Main Authors: Zhu Wu, Qiu Peng, Zongyao Ren, Xuemeng Xu, Xianjie Jiang, Wenjuan Yang, Yaqian Han, Linda Oyang, Jinguan Lin, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Qianjin Liao, Yujuan Zhou
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Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05553-5
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author Zhu Wu
Qiu Peng
Zongyao Ren
Xuemeng Xu
Xianjie Jiang
Wenjuan Yang
Yaqian Han
Linda Oyang
Jinguan Lin
Mingjing Peng
Nayiyuan Wu
Yanyan Tang
Qianjin Liao
Yujuan Zhou
author_facet Zhu Wu
Qiu Peng
Zongyao Ren
Xuemeng Xu
Xianjie Jiang
Wenjuan Yang
Yaqian Han
Linda Oyang
Jinguan Lin
Mingjing Peng
Nayiyuan Wu
Yanyan Tang
Qianjin Liao
Yujuan Zhou
author_sort Zhu Wu
collection DOAJ
description Abstract Many studies have reported an association between oral microbiota and oral cancer (OC). Yet, the causal relationship between oral microbiota and OC remains undetermined. This Mendelian randomization (MR) study utilized the most recent genome-wide association study of oral microbiota from the ADDITION-PRO study (n = 610, European ancestry), along with the summary statistics for OC from the UK Biobank consortium (643 cases and 406,821 controls, European ancestry). Instrumental variables were selected at P < 1 × 10⁻⁵, clumped for linkage disequilibrium (R² < 0.001, window size = 10,000 kb), filtered for minor allele frequency > 0.01, and F-statistic > 10 to ensure instrument strength. Inverse variance weighted, weighted model, MR-Egger, maximum likelihood, MR-PRESSO, and weighted median were used to assess the causal association between oral microbiota and OC. Reverse MR analysis was conducted on microbes causally linked to OC in the forward MR analysis. In inverse variance weighted estimates, Prevotella had a protective effect on OC (OR = 0.89, 95% CI: 0.81–0.99, P = 0.03), while Veillonella exhibited a deleterious effect on OC (OR = 1.14, 95% CI: 1.01–1.31, P = 0.04). Reverse MR analysis indicated no significant causal effect of OC on oral microbiota. In addition, instrumental variables did not show significant heterogeneity or horizontal pleiotropy. Our findings suggest that Prevotella and Veillonella were causally linked to OC. Further randomized controlled trials are necessary to elucidate the impact of oral microbiota on OC and their underlying mechanism.
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spelling doaj-art-9b0a71188e6e4e33b499a1f4cd72b43b2025-08-20T02:30:46ZengNature PortfolioScientific Reports2045-23222025-06-011511710.1038/s41598-025-05553-5Causal association between oral microbiota and oral cancer: a mendelian randomization studyZhu Wu0Qiu Peng1Zongyao Ren2Xuemeng Xu3Xianjie Jiang4Wenjuan Yang5Yaqian Han6Linda Oyang7Jinguan Lin8Mingjing Peng9Nayiyuan Wu10Yanyan Tang11Qianjin Liao12Yujuan Zhou13Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityDepartment of Oncology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal UniversityHunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityAbstract Many studies have reported an association between oral microbiota and oral cancer (OC). Yet, the causal relationship between oral microbiota and OC remains undetermined. This Mendelian randomization (MR) study utilized the most recent genome-wide association study of oral microbiota from the ADDITION-PRO study (n = 610, European ancestry), along with the summary statistics for OC from the UK Biobank consortium (643 cases and 406,821 controls, European ancestry). Instrumental variables were selected at P < 1 × 10⁻⁵, clumped for linkage disequilibrium (R² < 0.001, window size = 10,000 kb), filtered for minor allele frequency > 0.01, and F-statistic > 10 to ensure instrument strength. Inverse variance weighted, weighted model, MR-Egger, maximum likelihood, MR-PRESSO, and weighted median were used to assess the causal association between oral microbiota and OC. Reverse MR analysis was conducted on microbes causally linked to OC in the forward MR analysis. In inverse variance weighted estimates, Prevotella had a protective effect on OC (OR = 0.89, 95% CI: 0.81–0.99, P = 0.03), while Veillonella exhibited a deleterious effect on OC (OR = 1.14, 95% CI: 1.01–1.31, P = 0.04). Reverse MR analysis indicated no significant causal effect of OC on oral microbiota. In addition, instrumental variables did not show significant heterogeneity or horizontal pleiotropy. Our findings suggest that Prevotella and Veillonella were causally linked to OC. Further randomized controlled trials are necessary to elucidate the impact of oral microbiota on OC and their underlying mechanism.https://doi.org/10.1038/s41598-025-05553-5Mendelian randomization analysisMouth neoplasmsOral microbiotaCausal inference
spellingShingle Zhu Wu
Qiu Peng
Zongyao Ren
Xuemeng Xu
Xianjie Jiang
Wenjuan Yang
Yaqian Han
Linda Oyang
Jinguan Lin
Mingjing Peng
Nayiyuan Wu
Yanyan Tang
Qianjin Liao
Yujuan Zhou
Causal association between oral microbiota and oral cancer: a mendelian randomization study
Scientific Reports
Mendelian randomization analysis
Mouth neoplasms
Oral microbiota
Causal inference
title Causal association between oral microbiota and oral cancer: a mendelian randomization study
title_full Causal association between oral microbiota and oral cancer: a mendelian randomization study
title_fullStr Causal association between oral microbiota and oral cancer: a mendelian randomization study
title_full_unstemmed Causal association between oral microbiota and oral cancer: a mendelian randomization study
title_short Causal association between oral microbiota and oral cancer: a mendelian randomization study
title_sort causal association between oral microbiota and oral cancer a mendelian randomization study
topic Mendelian randomization analysis
Mouth neoplasms
Oral microbiota
Causal inference
url https://doi.org/10.1038/s41598-025-05553-5
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