Genetically predicted inflammatory protein mediate the association between lipidome and colon cancer
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...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-08-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-03367-5 |
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| Summary: | 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. |
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| ISSN: | 2730-6011 |