The role of blood metabolites in oral cancer - insights from a Mendelian randomization approach

Sep 21, 2026

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This original research explores the causal influence of blood metabolites on oral cancer using a two-sample Mendelian randomization framework. Genetic risk scores were constructed from UK Biobank individual-level and GWAS summary data to evaluate 486 blood metabolites. Multiple MR estimators, including inverse variance weighted, MR-Egger, and weighted median, were applied, with sensitivity checks using heterogeneity and pleiotropy assessments. Twenty-nine metabolites met selection criteria, including risk- and protective-associated metabolites. Findings support roles for specific metabolites and suggest value for diagnostic and therapeutic development, while requiring further validation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Aim

Materials and methods

Results

Conclusion

TYPE Original Research PUBLISHED 05 February 2024 DOI 10.3389/fonc.2024.1305684 OPEN ACCESS EDITED BY So Hee Kwon, Yonsei University, Republic of Korea REVIEWED BY Aishwarya Jala, Northwestern University, United States Zhe-Sheng Chen, St. John ’s University, United States *CORRESPONDENCE Ziyang Hu [pyx112233@163.com](pyx112233@163.com)[ ](pyx112233@163.com)Runzhi Deng [doctord@163.com](doctord@163.com)[ ](doctord@163.com)Zitong Lin [linzitong_710@163.com](linzitong_710@163.com) RECEIVED 09 October 2023 ACCEPTED 02 January 2024 PUBLISHED 05 February 2024 CITATION Hu Z, Xu Z, Yue Q, Pan X, Shi P, Zhang D, Zhang J, Deng R and Lin Z (2024) The role of blood metabolites in oral cancer: insights from a Mendelian randomization approach. Front. Oncol. 14:1305684 . doi: 10.3389/fonc.2024.1305684 COPYRIGHT © 2024 Hu, Xu, Yue, Pan, Shi, Zhang, Zhang, Deng and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The role of blood metabolites in oral cancer: insights from a Mendelian randomization approach Ziyang Hu 1*, Zhe Xu 1, Qu Yue 1, Xuhong Pan 1, Ping Shi 1, Dandan Zhang1, Jiexia Zhang1, Runzhi Deng 2* and Zitong Lin 3* 1Shenzhen Longhua District Central Hospital, Department of Stomatology, Shenzhen, China, 2 Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China, 3 Department of Dentomaxillofacial Radiology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China Aim: This research aimed to explore the causal impact of blood metabolites on oral cancer using a two-sample Mendelian randomization (MR) analysis. The study endeavored to identify potential biomarkers for oral cancer ’ s clinical management. Materials and methods: Based on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we ﬁrst constructed genetic risk scores (GRSs) of 486 human blood metabolites and evaluated the effect on oral cancer. Various statistical methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, among others, were employed to analyze the potential causal relationship between blood metabolites and oral cancer. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leaveone-out analyses, and MR-Egger intercept tests. Results: 29 metabolites met the stringent selection criteria. Out of these, 14 metabolites demonstrated a positive association with oral cancer risk, while 15 metabolites indicated a protective effect against oral cancer. The IVW-derived estimates were signiﬁcant, and the results were consistent across different statistical methodologies . Both the Cochran Q test and the MR-Egger intercept test indicated no heterogeneity and pleiotropy. Conclusion: This MR study offers evidence of the role speciﬁc blood metabolites play in oral cancer, pinpointing several with potential risk or protective effects. These ﬁndings could be helpful for new diagnostic tools and treatments for oral cancer. While the results are promising, additional research is necessary to fully validate and reﬁne these conclusions. This study serves as a foundational step towards more comprehensive understandings in the future. KEYWORDS Mendelian randomization, blood metabolites, oral cancer, genome-wide association study, SNPs, metabolomics Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) 1 Introduction Oral cancer, classiﬁed under head and neck malignancies, stands as the world’s sixth most common cancer, with o

FAQs

What is the study aim regarding oral cancer and blood metabolites?

The study aims to determine the causal impact of blood metabolites on oral cancer and identify potential biomarkers for clinical management.

How were causal effects evaluated in this research?

Using two-sample Mendelian randomization with genetic risk scores derived from UK Biobank and GWAS summary datasets, analyzed with multiple MR methods.

How many metabolites were identified as significant, and what did they indicate?

A total of 29 metabolites met the selection criteria: 14 were positively associated with oral cancer risk and 15 showed a protective effect.

Sep 21, 2026

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