Supplementary data of "Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks"

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.观察性研究与孟德尔随机化（Mendelian randomization, MR）已证实血脂异常与部分癌症易感性存在关联。然而，目前仍缺乏对覆盖多种癌症类型的因果关联的全面探索。本研究开展两样本孟德尔随机化分析，以阐明9种血脂代谢谱指标——即脂联素、瘦素、脂蛋白A（Lipoprotein A）、载脂蛋白A1（apolipoprotein A1）、载脂蛋白B（apolipoprotein B）、总胆固醇、甘油三酯、低密度脂蛋白胆固醇（LDL-cholesterol）与高密度脂蛋白胆固醇（HDL-cholesterol）——与21种特定部位癌症风险之间的因果联系。研究结果显示，遗传预测的脂联素水平升高与卵巢癌风险降低相关；而遗传确定的瘦素水平升高会增加膀胱癌风险，但降低前列腺癌风险。脂蛋白A会升高前列腺癌风险，却降低子宫内膜癌风险；载脂蛋白A1则会升高乳腺癌与宫颈癌风险。此外，总胆固醇水平升高与肾癌呈正相关，甘油三酯与非黑色素瘤皮肤癌呈正相关，但与乳腺癌呈负相关。本研究还观察到，遗传预测的低密度脂蛋白胆固醇（LDL-cholesterol）对子宫内膜癌具有保护作用，而高密度脂蛋白胆固醇（HDL-cholesterol）对乳腺癌存在不良影响。本研究明确证实血脂代谢谱对癌症易感性存在因果效应，为癌症预防提供了更为坚实的证据，并引发了对人类群体未来健康的思考。