Causal association between blood metabolites and head and neck cancer: butyrylcarnitine identified as an associated trait for cancer risk and progression.

BACKGROUND: Blood metabolites play an important role in predicting or influencing the occurrence and development of cancers. We aimed to evaluate the relationship between blood metabolites and the occurrence of head and neck cancer (HNC). METHODS: We employed a Mendelian randomization (MR) approach to investigate the role of blood metabolites in HNC predisposition. The HNC cell line HN30 was treated with butyrylcarnitine, the metabolite identified through MR analysis, and subjected to a series of cellular assays to assess its potential carcinogenic effects. RESULTS: Among the 258 blood metabolites analyzed, butyrylcarnitine emerged as the only metabolite demonstrating a potential causal association with HNC risk following Bonferroni correction (inverse-variance-weighted MR method: β = 0.904, P < 0.001). Genetically predicted higher levels of butyrylcarnitine (log-transformed) were causally linked to an increased risk of HNC (OR: 2.470, 95% CI: 1.530-3.987). Sensitivity analyses, including MR-Egger regression, leave-one-out analysis, and funnel plots, confirmed the robustness of the findings, with no evidence of directional pleiotropy. In vitro experiments further demonstrated that butyrylcarnitine promoted the proliferation, migration and invasion of HN30 cells. CONCLUSIONS: By employing a genetic epidemiological framework, our research assessed the impact of metabolite butyrylcarnitine on HNC susceptibility. These findings offer valuable insights into potential therapeutic targets and highlight the promise of targeted metabolic strategies for reducing HNC risk. Nevertheless, further research is required to elucidate the precise biological mechanisms underlying these findings.