Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer

BackgroundEvidence supports an observational association between the gut microbiome and susceptibility to extraintestinal cancers, but the causal relationship of this association remains unclear.MethodsTo identify the specific causal gut microbiota of oral and oropharyngeal cancer, we performed two-...

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Main Authors: Qihe Zhang, Huanhuan Wang, Yuan Tian, Jinjie Li, Ying Xin, Xin Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1210807/full
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author Qihe Zhang
Huanhuan Wang
Huanhuan Wang
Huanhuan Wang
Yuan Tian
Jinjie Li
Ying Xin
Xin Jiang
Xin Jiang
Xin Jiang
author_facet Qihe Zhang
Huanhuan Wang
Huanhuan Wang
Huanhuan Wang
Yuan Tian
Jinjie Li
Ying Xin
Xin Jiang
Xin Jiang
Xin Jiang
author_sort Qihe Zhang
collection DOAJ
description BackgroundEvidence supports an observational association between the gut microbiome and susceptibility to extraintestinal cancers, but the causal relationship of this association remains unclear.MethodsTo identify the specific causal gut microbiota of oral and oropharyngeal cancer, we performed two-sample Mendelian randomization (MR) analysis of gut microbiota on oral and oropharyngeal cancer using a fixed-effects inverse-variance-weighted model. Gut microbiota across five different taxonomical levels from the MiBioGen genome-wide association study (GWAS) were used as exposures. Oral cancer, oropharyngeal cancer and a combination of the two cancers defined from three separate data sources were used as the outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher abundance of microbiome.Results & ConclusionsThere was little evidence for a causal effect of gut microbiota on oral and oropharyngeal cancer when using a genome-wide p-value threshold for selecting instruments. Secondary analyses using a more lenient p-value threshold indicated that there were 90 causal relationships between 58 different microbial features but that sensitivity analyses suggested that these were possibly affected by violations of MR assumptions and were not consistent across MR methodologies or data sources and therefore are also to unlikely reflect causation. These findings provide new insights into gut microbiota-mediated oral and oropharyngeal cancers and warrant further investigation.
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spelling doaj.art-db225f3ec22942e2b6644e0835f6511a2024-01-04T04:59:18ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-01-011310.3389/fcimb.2023.12108071210807Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancerQihe Zhang0Huanhuan Wang1Huanhuan Wang2Huanhuan Wang3Yuan Tian4Jinjie Li5Ying Xin6Xin Jiang7Xin Jiang8Xin Jiang9Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaJilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaDepartment of Radiation Oncology, The First Hospital of Jilin University, Changchun, ChinaNHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, ChinaKey Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaKey Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaKey Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaJilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, ChinaDepartment of Radiation Oncology, The First Hospital of Jilin University, Changchun, ChinaNHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, ChinaBackgroundEvidence supports an observational association between the gut microbiome and susceptibility to extraintestinal cancers, but the causal relationship of this association remains unclear.MethodsTo identify the specific causal gut microbiota of oral and oropharyngeal cancer, we performed two-sample Mendelian randomization (MR) analysis of gut microbiota on oral and oropharyngeal cancer using a fixed-effects inverse-variance-weighted model. Gut microbiota across five different taxonomical levels from the MiBioGen genome-wide association study (GWAS) were used as exposures. Oral cancer, oropharyngeal cancer and a combination of the two cancers defined from three separate data sources were used as the outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher abundance of microbiome.Results & ConclusionsThere was little evidence for a causal effect of gut microbiota on oral and oropharyngeal cancer when using a genome-wide p-value threshold for selecting instruments. Secondary analyses using a more lenient p-value threshold indicated that there were 90 causal relationships between 58 different microbial features but that sensitivity analyses suggested that these were possibly affected by violations of MR assumptions and were not consistent across MR methodologies or data sources and therefore are also to unlikely reflect causation. These findings provide new insights into gut microbiota-mediated oral and oropharyngeal cancers and warrant further investigation.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1210807/fullgut microbiomeoral canceroropharyngeal cancerMendelian randomizationmeta-analysis
spellingShingle Qihe Zhang
Huanhuan Wang
Huanhuan Wang
Huanhuan Wang
Yuan Tian
Jinjie Li
Ying Xin
Xin Jiang
Xin Jiang
Xin Jiang
Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
Frontiers in Cellular and Infection Microbiology
gut microbiome
oral cancer
oropharyngeal cancer
Mendelian randomization
meta-analysis
title Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
title_full Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
title_fullStr Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
title_full_unstemmed Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
title_short Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
title_sort mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
topic gut microbiome
oral cancer
oropharyngeal cancer
Mendelian randomization
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1210807/full
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