Causal relationship between circulating lipid metabolism biomarkers and tongue cancer: A two-sample Mendelian...

This study aimed to investigate the potential causal relationship between lipid metabolism biomarkers and the risk of tongue cancer, providing a theoretical basis for future prevention and treatment strategies. A two-sample Mendelian randomization (MR) analysis was performed using large-scale genome-wide association study datasets to examine the causal relationship between 233 circulating metabolic markers and tongue cancer. Multiple MR methods were employed, including inverse-variance weighted, MR-Egger, weighted median, and Bayesian weighted MR. Sensitivity analyses were conducted to assess horizontal pleiotropy and heterogeneity, ensuring the robustness of the results. Genetically predicted higher levels of saturated fatty acids relative to total fatty acids, the ratio of phospholipids to total lipids in small very-low-density lipoproteins, and various cholesterol components in medium high-density lipoproteins (free cholesterol-to-total lipids, total cholesterol, and cholesterol esters in mHDL) were significantly associated with an increased risk of tongue cancer. Sensitivity analyses confirmed the stability and reliability of these associations. This study is the first to reveal a potential causal relationship between specific lipid metabolism biomarkers and tongue cancer. Notably, genetically elevated saturated fatty acids relative to total fatty acids ratios, cholesterol components in HDL (free cholesterol-to-total lipids, total cholesterol, and cholesterol esters in mHDL), and phospholipids to total lipids in small very-low-density lipoproteins were significantly associated with increased tongue cancer risk. Future research should focus on validating these findings in diverse populations and elucidating the underlying biological mechanisms, with the aim of developing early warning tools and potential intervention targets.