Tang Ning, Tang Jincheng, Zhang Jingting, Chen Hongyao, Yang Renyi
The First Hospital of Hunan University of Chinese Medicine, Hunan, China.
Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Hunan Academy of Chinese Medicine, Hunan, China.
Medicine (Baltimore). 2025 Aug 15;104(33):e43900. doi: 10.1097/MD.0000000000043900.
This study explores the causal relationship between plasma lipidome and 6 common cancers using Mendelian randomization. Genome-wide association study data on 179 lipid species were used as exposures, with genome-wide association study datasets for 6 cancers as outcomes. The primary method was inverse variance weighted analysis, supplemented by Mendelian randomization-Egger regression and weighted median approaches. Sensitivity analyses, including the Steiger test, were conducted to evaluate the directionality and robustness of the causal relationships. Key findings identified phosphatidylethanolamine (16:0_20:4) as a risk factor for hepatic cancer, while sphingomyelin (d40:1) was protective. For lung cancer, sterol ester (27:1/20:4) increased risk, whereas sterol ester (27:1/18:2) reduced it. Sterol ester (27:1/20:3) was a risk factor for colorectal cancer, while phosphatidylcholine (18:2_0:0) was protective. Phosphatidylcholine (16:0_20:4) increased esophageal cancer risk, while phosphatidylcholine (16:0_18:3) offered protection. Phosphatidylinositol (18:0_20:4) increased thyroid cancer risk, while phosphatidylinositol (16:0_18:2) was protective. Diacylglycerol (18:1_18:2) was protective against breast cancer. These findings shed light on the causal link between lipid metabolism and cancer risk, contributing to the understanding of lipid involvement in cancer pathogenesis and offering potential strategies for early detection and treatment.
本研究采用孟德尔随机化方法探讨血浆脂质组与6种常见癌症之间的因果关系。将179种脂质种类的全基因组关联研究数据用作暴露因素，6种癌症的全基因组关联研究数据集作为结果。主要方法是逆方差加权分析，并辅以孟德尔随机化-伊格回归和加权中位数方法。进行了包括斯泰格检验在内的敏感性分析，以评估因果关系的方向性和稳健性。主要发现确定磷脂酰乙醇胺（16:0_20:4）是肝癌的危险因素，而鞘磷脂（d40:1）具有保护作用。对于肺癌，甾醇酯（27:1/20:4）增加风险，而甾醇酯（27:1/18:2）降低风险。甾醇酯（27:1/20:3）是结直肠癌的危险因素，而磷脂酰胆碱（18:2_0:0）具有保护作用。磷脂酰胆碱（16:0_20:4）增加食管癌风险，而磷脂酰胆碱（16:0_18:3）具有保护作用。磷脂酰肌醇（18:0_20:4）增加甲状腺癌风险，而磷脂酰肌醇（16:0_18:2）具有保护作用。二酰基甘油（18:1_18:2）对乳腺癌具有保护作用。这些发现揭示了脂质代谢与癌症风险之间的因果联系，有助于理解脂质在癌症发病机制中的作用，并为早期检测和治疗提供潜在策略。
