Exploring the potential causal relationship between fatty acid metabolism ratios and major salivary gland carcinomas: A two-sample Mendelian randomization study

Major salivary gland carcinomas (MSGCs) is a rare but aggressive cancer, with limited understanding of its metabolic underpinnings. Lipid metabolism, particularly fatty acid metabolism ratios (FAMRs), has been implicated in various cancers, but its role in MSGCs remains unclear. This study aims to explore the potential causal relationships between specific FAMRs and MSGCs using Mendelian randomization (MR) analysis. A 2-sample MR analysis was conducted using summary data from genome-wide association studies. Three FAMRs, including the ratio of diacylglycerol to triglycerides (DAG/TG), total cholesterol (TC) to total lipids (TL) ratio in large very low-density lipoprotein (VLDL; TC/TL in large VLDL), and triglycerides to total lipids ratio in medium VLDL (TG/TL in medium VLDL), were investigated for their potential causal relationships with MSGCs. Sensitivity analyses, including MR-Egger and leave-one-out tests, were performed to assess pleiotropy and the robustness of the results. The DAG/TG and TC/TL ratios in large VLDL were significantly positively associated with an increased risk of MSGCs (OR = 10.921, P = .004 and OR = 2.651, P = .047, respectively). In contrast, the TG/TL ratio in medium VLDL showed a significant negative association with MSGCs risk (OR = 0.460, P = .041). Sensitivity analyses confirmed the robustness of these associations, with no evidence of significant pleiotropy in 2 of the ratios. This study reveals novel insights into the metabolic basis of MSGCs, demonstrating significant associations between specific FAMRs and MSGCs risk. These findings highlight the potential clinical relevance of FAMRs as biomarkers or therapeutic targets in MSGCs. Future studies should focus on diverse populations and mechanistic research to validate these associations and explore their clinical implications.