代谢综合征及其组分与消化系统恶性肿瘤的因果关联:两样本孟德尔随机化研究

doi:10.6040/j.issn.1671-7554.0.2024.0658

摘要/Abstract

摘要： 目的采用两样本孟德尔随机化(two-sample Mendelian randomization, TSMR)方法,从遗传学角度探索代谢综合征(metabolic syndrome, MetS)及其组分与消化系统恶性肿瘤之间的因果关联,为后者的预防提供新线索。方法基于全基因组关联研究(genome wide association study, GWAS)的汇总数据,将MetS及其组分作为暴露因素,消化系统恶性肿瘤作为结局变量,采用逆方差加权法(inverse variance weighted, IVW)为主要分析方法,加权中位数(weighted median, WM)和MR-Egger为补充分析方法评估因果效应;采用敏感性分析验证研究结果的可靠性。结果 IVW结果显示, MetS与肝癌(OR=1.357, 95%CI=1.004~1.834, P=0.047)和食管癌(OR=1.001, 95%CI=1.000~1.001, P=0.037)的发生风险增加相关。MetS各组分中,腰围(waist circumference, WC)与胃癌(OR=1.809, 95%CI=1.024~3.196, P=0.041)和食管癌(OR=1.001, 95%CI=1.000~1.002, P=0.020)的发生风险增加相关;高密度脂蛋白(high density lipoprotein, HDL)与结直肠癌(OR=0.789, 95%CI=0.633~0.984, P=0.035)的发生风险降低相关;敏感性分析提示研究结果稳健。结论 MetS会增加肝癌及食管癌的发生风险。在其各组分中,WC是胃癌及食管癌的发生危险因素,HDL结直肠癌发生的保护因素。

关键词: 孟德尔随机化, 代谢综合征, 消化系统恶性肿瘤, 全基因组关联研究, 因果关联

Abstract: Objective To provide new clues for the prevention and treatment of digestive system malignancies by using two sample Mendelian randomization(TSMR)method so as to explore the causal relationship between metabolic syndrome(MetS)and its components and digestive system malignancies from a genetic perspective. Methods Based on the summary data of genome-wide association study(GWAS), MetS and its components were used as exposure factors, and digestive system maligancies were used as outcome variables. The inverse variance weighted(IVW)method was used as the main analysis method, and weighted median(WM)and MR Egger were used as supplementary analysis methods to evaluate causal effects. The sensitivity analysis was used to verify the reliability of the research results. Results The IVW method showed that MetS is associated with an increased risk of liver cancer(OR=1.357, 95%CI=1.004-1.834, P=0.047)and esophageal cancer(OR=1.001, 95%CI=1.000-1.001, P=0.037). Among the components of MetS, waist circumference(WC)is associated with an increased risk of gastric cancer(OR=1.809, 95%CI=1.024-3.196, P=0.041)and esophageal cancer(OR=1.001, 95%CI=1.000-1.002, P=0.020); High density lipoprotein(HDL)is associated with a reduced risk of colorectal cancer(OR=0.789, 95%CI=0.633-0.984, P=0.035); Sensitivity analysis suggests that the research results are robust. Conclusion MetS increases the risk of liver and esophageal cancer, with WC being a risk factor for gastric and esophageal cancer, while HDL is a protective factor for colorectal cancer.

Key words: Mendelian randomization, Metabolic syndrome, Digestive system malignancies, Genome wide association study, Causal association

中图分类号:

R735

黄馨,王梦雪,付书璠,张琦悦,徐力. 代谢综合征及其组分与消化系统恶性肿瘤的因果关联:两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(5): 86-94.

HUANG Xin, WANG Mengxue, FU Shufan, ZHANG Qiyue, XU Li. Causal association of metabolic syndrome and its components with digestive system malignancies: a two-sample Mendelian randomized study[J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 86-94.

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