Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study

Introduction and aims: This study aimed to examine the causal link between oral microbiome and the risk of oral and oropharyngeal squamous cell carcinoma (OOPSCC) using Mendelian randomization (MR). Methods: Utilizing single nucleotide polymorphisms as instrumental variables, we applied the MR inver...

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Main Authors: Zhengrui Li, Xufeng Huang, Qi Wang, Divya Gopinath
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:International Dental Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S0020653925000395
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author Zhengrui Li
Xufeng Huang
Qi Wang
Divya Gopinath
author_facet Zhengrui Li
Xufeng Huang
Qi Wang
Divya Gopinath
author_sort Zhengrui Li
collection DOAJ
description Introduction and aims: This study aimed to examine the causal link between oral microbiome and the risk of oral and oropharyngeal squamous cell carcinoma (OOPSCC) using Mendelian randomization (MR). Methods: Utilizing single nucleotide polymorphisms as instrumental variables, we applied the MR inverse-variance weighted approach to assess the impact of salivary and tongue microbiome on OOPSCC. The data were obtained from the CNGBdb database and the UK Biobank, and analytical procedures were performed using the R package ‘TwoSampleMR’. To ensure the robustness of our findings, we conducted sensitivity studies, which included the MR-Egger intercept test, to establish strong correlations and eliminate the phenomenon of horizontal pleiotropy. Result: Our large-scale MR study revealed a genetically predisposed causal relationship between 13 microbial taxa, each from saliva and tongue, with OOPSCC. Notably, microbial taxa from six genera, including Prevotella, Neisseria, Veillonella, Granulicatella, Treponema, and Streptococcus, in both salivary and tongue microbiomes, showed this relationship. Conversely, several taxa, including Hemophilus, Solobacterium, Campylobacter, and Porphyromonas, predominantly demonstrated an inverse relationship, suggesting a protective effect. The robustness of our findings was further confirmed through sensitivity analyses, providing additional confidence in our results. Conclusion: Our MR study indicates that the oral microbiota has a significant causal impact on the risk of oral and oropharyngeal cancers. The microbial biomarkers we identified, which are linked to OOPSCC, have the potential to uncover the underlying mechanisms and pave the way for new therapeutic approaches for targeted treatment of these malignancies.
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spelling doaj-art-ca0be00a01b741f091f49ee7b11f5f7c2025-08-20T03:49:03ZengElsevierInternational Dental Journal0020-65392025-06-017531897190510.1016/j.identj.2025.01.017Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization StudyZhengrui Li0Xufeng Huang1Qi Wang2Divya Gopinath3Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaFaculty of Dentistry, University of Debrecen, Debrecen, HungaryDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBasic Medical and Dental Sciences Department, College of Dentistry, Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; Corresponding author at: Basic Medical and Dental Sciences Department, College of Dentistry, Ajman University, Ajman PO Box 346, United Arab Emirates.Introduction and aims: This study aimed to examine the causal link between oral microbiome and the risk of oral and oropharyngeal squamous cell carcinoma (OOPSCC) using Mendelian randomization (MR). Methods: Utilizing single nucleotide polymorphisms as instrumental variables, we applied the MR inverse-variance weighted approach to assess the impact of salivary and tongue microbiome on OOPSCC. The data were obtained from the CNGBdb database and the UK Biobank, and analytical procedures were performed using the R package ‘TwoSampleMR’. To ensure the robustness of our findings, we conducted sensitivity studies, which included the MR-Egger intercept test, to establish strong correlations and eliminate the phenomenon of horizontal pleiotropy. Result: Our large-scale MR study revealed a genetically predisposed causal relationship between 13 microbial taxa, each from saliva and tongue, with OOPSCC. Notably, microbial taxa from six genera, including Prevotella, Neisseria, Veillonella, Granulicatella, Treponema, and Streptococcus, in both salivary and tongue microbiomes, showed this relationship. Conversely, several taxa, including Hemophilus, Solobacterium, Campylobacter, and Porphyromonas, predominantly demonstrated an inverse relationship, suggesting a protective effect. The robustness of our findings was further confirmed through sensitivity analyses, providing additional confidence in our results. Conclusion: Our MR study indicates that the oral microbiota has a significant causal impact on the risk of oral and oropharyngeal cancers. The microbial biomarkers we identified, which are linked to OOPSCC, have the potential to uncover the underlying mechanisms and pave the way for new therapeutic approaches for targeted treatment of these malignancies.http://www.sciencedirect.com/science/article/pii/S0020653925000395Oral microbiomeMendelian randomisationGeneticsCausalRisk factor
spellingShingle Zhengrui Li
Xufeng Huang
Qi Wang
Divya Gopinath
Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
International Dental Journal
Oral microbiome
Mendelian randomisation
Genetics
Causal
Risk factor
title Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
title_full Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
title_fullStr Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
title_full_unstemmed Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
title_short Causal Association Between Microbiome and Oral-Oropharyngeal Cancer: A Mendelian Randomization Study
title_sort causal association between microbiome and oral oropharyngeal cancer a mendelian randomization study
topic Oral microbiome
Mendelian randomisation
Genetics
Causal
Risk factor
url http://www.sciencedirect.com/science/article/pii/S0020653925000395
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