【摘要】 目的 利用孟德尔随机化（Mendelian randomization, MR）的研究方法，探讨代谢综合征（metabolic syndrome, MetS）组成部分与子宫内膜癌的因果关联。方法 对全基因组关联研究数据库（Genome-Wide Association Studies, GWAS）进行数据挖掘，暴露因素为MetS组成部分（血脂、血压、血糖和肥胖），结局因素为子宫内膜癌。借助MREgger法、加权中位数法、逆方差加权法（inverse variance weighting, IVW）等回归模型进行MR分析，以比值比（odds ratio,OR）评价MetS组成部分与子宫内膜癌的因果关系。对正向MR分析中发现的与子宫内膜癌有因果关系的MetS组成部分进行反向MR分析。结果 IVW结果经Benjamini-Hochberg校正试验后显示多个MetS组分（肥胖、血脂、血压及血糖）均与子宫内膜癌存在因果关联。其中，肥胖的3个组分体质量指数、超重及体脂率均与子宫内膜癌的风险增加具有因果关联（P<0.001,OR>1）；血脂中高胆固醇水平（P<0.001,OR<1）、高甘油三酯水平及高磷脂水平等与子宫内膜癌风险降低有因果关联（P<0.05,OR<1）；血压中心脏病、动脉粥样硬化及卒中等与子宫内膜癌风险降低有因果关联（P<0.05,OR<1）；血糖中低空腹胰岛素水平、1型糖尿病、胰岛素抵抗及高糖化血红蛋白水平与子宫内膜癌风险降低有因果关联（P<0.05,OR<1）,2型糖尿病及高空腹胰岛素水平与子宫内膜癌风险增加有因果关联（P<0.05,OR>1）。在反向MR分析中，没有证据表明上述阳性的MetS组分与子宫内膜癌存在反向因果关系。结论 MR研究提示肥胖和2型糖尿病是子宫内膜癌的危险因素，而MetS的其他组分，如高血脂、心脑血管疾病、胰岛素抵抗及糖尿病合并症等是子宫内膜癌的保护因素。尚需进一步研究以阐明MetS与子宫内膜癌之间的关联，并进一步探索其中的潜在机制。更多还原

【Abstract】 Objective To investigate the causal associations between components of metabolic syndrome(MetS) and endometrial carcinoma using Mendelian randomization(MR). Methods Data mining of the Genome-Wide Association Studies(GWAS) database was performed, with the exposure factors being MetS components(lipids, blood pressure, blood glucose, and obesity) and the outcome factor being endometrial carcinoma. MR analyses were performed with the help of regression models, including MR-Egger method, weighted median method, and inverse variance weighted(IVW) method, and the causal relationship between MetS components and endometrial carcinoma was evaluated by odds ratio(OR). Reverse MR analysis was performed for the MetS components found to have a causal relationship with endometrial carcinoma in the forward MR analysis. Results After applying Benjamini-Hochberg correction, IVW results showed a causal relationship between multiple MetS components(obesity, lipids, blood pressure, and blood glucose) and endometrial carcinoma. Specifically, the three components of obesity, including body mass index,overweight, and percentage of body fat, were causally associated with an increased risk of endometrial carcinoma(P<0.001, OR>1). In blood lipids, high cholesterol levels(P<0.001, OR<1), high triglyceride levels, and high phospholipid levels were causally associated with a reduced risk of endometrial carcinoma(P<0.05, OR<1). Regarding blood pressure,heart disease, atherosclerosis, and stroke were causally associated with a reduced risk of endometrial carcinoma(P<0.05,OR<1). Regarding blood glucose, low fasting insulin levels, type 1 diabetes mellitus, insulin resistance, and high glycated hemoglobin levels were causally associated with a reduced risk of endometrial carcinoma(P<0.05, OR<1), while type 2diabetes mellitus and high fasting insulin levels were causally associated with an increased risk of endometrial carcinoma(P<0.05, OR>1). Reverse MR analysis did not produce any evidence for a reverse causality between the above positive MetS components and endometrial carcinoma. Conclusion The MR study suggests that obesity and type 2 diabetes mellitus are risk factors for endometrial carcinoma, while other MetS components, including hyperlipidemia,cardiovascular diseases, insulin resistance, and complications of diabetes mellitus, are protective factors for endometrial carcinoma. Further research is needed to clarify the association between MetS and endometrial carcinoma and to further explore the underlying mechanisms involved.更多还原