Abstract
BACKGROUND: Previous studies show correlations between colon cancer, dyslipidemia, and inflammatory proteins. However, the exact causal relationships are still unclear and no comprehensive analysis exists. METHODS: We used a two-sample Mendelian Randomization (MR) strategy to assess the link between lipidomes and colon cancer risk. Bayesian Weighted Mendelian Randomization (BWMR) and MR-robust adjusted profile score (MR-RAPS) were employed to validate our findings. Furthermore, inverse MR analysis was conducted to investigate the possibility of reverse causation. Through a comprehensive two-step MR analysis, we identified the mediating effect of inflammatory factors. Various sensitivity analyses were carried out to ensure the reliability and robustness of our results. RESULTS: Our MR analysis highlighted negative correlations between Phosphatidylcholine (O-16:1_18:0) (OR, 95% CI 0.771, (0.610, 0.975)), Phosphatidylethanolamine (O-16:1_22:5) (OR, 95% CI 0.788, (0.664, 0.934)), Phosphatidylethanolamine (O-18:1_18:2) (OR, 95% CI 0.825, (0.708, 0.960)) and colon cancer. In contrast, we found positive correlations with Sterol ester (27:1/18:3) (OR, 95% CI 1.278, (1.068, 1.530)), Phosphatidylcholine (18:0_22:5) (OR, 95% CI 1.322, (1.118, 1.563)), Triacylglycerol (46:1) (OR, 95% CI 1.272, (1.047, 1.546)), Triacylglycerol (46:2) (OR, 95% CI 1.236, (1.034, 1.478)) and colon cancer. Furthermore, mediation analysis revealed that a fraction of the impacts of Phosphatidylcholine (18:0_22:5) and Phosphatidylethanolamine (O-16:1_22:5) on colon cancer were mediated by TNF-related apoptosis-inducing ligand levels. CONCLUSION: This study presents evidence supporting potential causal correlations between 7 lipidome levels and colon cancer, based on Mendelian randomization analyses. Additionally, inflammatory factors mediate some of these effects.