Abstract:
The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran\'s Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000-1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000-1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer.
摘要:
血脂水平与膀胱癌之间的因果关系目前仍不确定。我们的目的是揭示甘油三酯之间的因果关系,HDL,通过单变量和多变量孟德尔随机化(MR)分析,LDL和膀胱癌的风险。暴露的单核苷酸多态性(SNP)(甘油三酸酯:441,016个样品;HDL:403,943个样品;LDL:440,546个样品)从英国生物银行获得。与膀胱癌相关的遗传变异包括1554例和359,640例对照。单变量和多变量MR方法进行了后续分析,吸烟被认为是一种困惑。逆方差加权(IVW),MR-Egger,加权中位数法,Cochran的Q测试,和MR-PRESSO被认为是主要的MR分析和敏感性分析方法。单变量MR分析结果表明,甘油三酯水平(P=0.011,OR=1.001,95%CI=1.000-1.002)与膀胱癌风险增加有因果关系。多变量MR结果表明,在调整HDL的影响后,较高的甘油三酯水平仍然会增加膀胱癌的风险。LDL,吸烟(P=0.042,OR=1.001,95%CI=1.000-1.002)。我们的发现支持甘油三酯水平在遗传水平上与LDL和HDL无关,与膀胱癌风险增加有因果关系。及时关注血脂水平的变化可能会降低膀胱癌的风险。