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

Abstract

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, leave-one-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; SNPs; blood metabolites; genome-wide association study; metabolomics; oral cancer.