杜疑,女,硕士在读,主要从事外科甲乳方向研究,ORCID: 0009-0006-3256-0733
孙海东,男,博士,主任医师,主要从事外科甲乳方向研究,E-mail: Shd02@163.com,ORCID: 0009-0000-5922-5990
纸质出版:2026
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杜疑, 薛梦瑶, 陈慧颖, 孙颖, 罗天裕, 孙海东. 代谢综合征与乳腺癌:一项双向两样本孟德尔随机化研究的因果推断[J]. 肿瘤防治研究, 2026, 53(4): 267-273.
DU Yi, XUE Mengyao, CHEN Huiying, et al. Causal Inference on Association Between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization Study[J]. 2026, 53(4): 267-273.
杜疑, 薛梦瑶, 陈慧颖, 孙颖, 罗天裕, 孙海东. 代谢综合征与乳腺癌:一项双向两样本孟德尔随机化研究的因果推断[J]. 肿瘤防治研究, 2026, 53(4): 267-273. DOI: 10.3971/j.issn.1000-8578.2026.25.0696.
DU Yi, XUE Mengyao, CHEN Huiying, et al. Causal Inference on Association Between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization Study[J]. 2026, 53(4): 267-273. DOI: 10.3971/j.issn.1000-8578.2026.25.0696.
目的
采用双向两样本孟德尔随机化方法探讨代谢综合征与乳腺癌之间的因果关联。
方法
分别从IEU GWAS数据库和GWAS catalog数据库获取代谢综合征与乳腺癌的全基因组关联研究汇总数据,人群涉及美国与东亚。研究采用双向因果设计:首先以代谢综合征为暴露、乳腺癌为结局进行正向分析,再互换进行反向分析。主要采用逆方差加权法进行效应估计,并以MR-Egger回归、加权中位数法、简单模式法和加权模式法作为补充。工具变量强度通过F统计量(F10)进行筛选,并通过异质性检验、水平多效性检验、森林图和留一法敏感性分析评估结果的稳健性。
结果
逆方差加权法分析结果显示,代谢综合征与乳腺癌之间未见显著的因果关系(
OR
=1.00,95%
CI
: 0.97~1.03,
P
0.05)。敏感性分析结果一致,表明本研究结论具有较好的稳健性。
结论
本研究未发现代谢综合征与乳腺癌之间存在正向或反向因果关系的证据。
Objective
To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach.
Methods
Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog
with populations encompassing the United States and East Asi
a. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome
followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation
supplemented by MR-Egger regression
the weighted median method
the simple mode method
and the weighted mode method. Instrument variable strength was screened using the F-statistic (F10). Robustness of the results was assessed through heterogeneity tests
horizontal pleiotropy tests
forest plots
and leave-one-out sensitivity analyses.
Results
The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (
OR
=1.00
95%
CI
: 0.97-1.03)
P
0.05). Sensitivity analyses yielded consistent results
suggesting the good robustness of the study findings.
Conclusion
This study found no evidence to support a causal relationship
either positive or negative
between metabolic syndrome and breast cancer.
Bray F, Laversanne M, Sung H, et al . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2024, 74(3): 229-263.
Yue L, Dong MJ, Zhao XL, et al. Current status, challenges, and countermeasures of prevention andcontrol of breast cancer in China[J]. Zhongguo Gong Gong Wei Sheng, 2025, 41(12): 1527-1531.
Huang WS, Xu JY, Yan F. Analysis of the influencing factors of central obesity on the incidence of breast cancer in women[J]. Zhonghua Zhong Liu Fang Zhi Za Zhi, 2023, 30(4): 219-224.
Ge PT, Chen WL, Dai KP. Survival status of women with breast cancer in different ages[J]. Zhongguo Yi Xue Gong Cheng, 2022, 30(4): 36-40.
Mohammed AM, Hamed HB, Noaman MK, et al . Metabolic syndrome and breast cancer risk[J ] . J Egypt Natl Canc Inst, 2023, 35(1): 42.
Xu Y. Analysis of the effect of type 2 diabetes on endometrialcarcinoma[D]. Jingzhou: Yangtze University, 2024.
Lu Y, Dai SL, Wang MJ, et al. The relationship between the triglyceride-glucose index and its modified index and colorectal cancer: A prospective cohort study[J]. Shi Yong Yi Xue Za Zhi, 2025, 41(15): 2362-2371.
Li F, Simon MC. Cancer Cells Don't Live Alone: Metabolic Communication within Tumor Microenvironments[J]. Dev Cell, 2020, 54(2): 183-195.
Leng WL. Effect and Mechanism of Metformin on Breast Density in Over weight/obese Premenopausal Women and the Breast Tumor-Associated Adipose Microenvironment[D]. Chongqing: Army Medical University, 2023.
Hu WJ, Ying X. The Impact of Diverse Antineoplastic Chemotherapeutic Agents on Glycometabolism in Breast Cancer Patients[J]. Jiangxi Yi Yao, 2021, 56(5): 669-671.
Liu TR, Ao XD, Liang JQ. The specific roles of adipose tissue in breast cancer[J]. Sheng Ming Ke Xue, 2025. [Epub ahead of print].
Liu YD, Zhang YX, Li LH. The carcinogenic roles and mechanisms of energy metabolism reprogramming inbreast cancer[J]. Zhongguo Zhong Liu Sheng Wu Zhi Liao Za Zhi, 2025, 32(8): 870-880.
Zhang YC, Shi JQ, Zhang YJ, et al. Advances in synergistic therapies targeting metabolic mechanisms and the immune microenvironment in breast cancer[J]. Ji Chu Yi Xue Yu Lin Chuang, 2025, 45(12): 1662-1667.
Esposito K, Chiodini P, Colao A, et al . Metabolic syndrome and risk of cancer: a systematic review and meta-analysis[J ] . Diabetes Care, 2012, 35(11): 2402-2411.
Bai HR, Pang JZ. Proposal and Clinical Status of Cardiovascular-Kidney-Metabolic Syndrome[J]. Xin Xue Guan Bing Xue Jin Zhan, 2025, 46(12): 1071-1075.
Yu JL. A study of the key associations between the metabolic syndromepopulation and the pathogenesis of the stroke risk population[D]. Changchun: Changchun University of Chinese Medicine, 2023.
Li X, Zhai Y, Zhao J, et al . Impact of Metabolic Syndrome and It's Components on Prognosis in Patients With Cardiovascular Diseases: A Meta-Analysis[J ] . Front Cardiovasc Med, 2021, 8: 704145.
Zhou J. Association of Different Metabolic Obesity Phenotypeswith Breast Cancer Risk in Women[D]. Tangshan: North China University of Science and Technology, 2024.
Sureka N, Chohan S, Zaheer S, et al . Matter of Fat: Cancer-Associated Adipocytes as Mediators of Tumor Progression and Immune Evasion[J ] . Cell Biol Int, 2025, 49(12): 1591-1616.
Zhang L, Liu S, Yue G, et al . The causality between Type 2 diabetes and breast cancer: a bidirectional two-sample Mendelian randomization study[J ] . Future Oncol, 2024, 20(18): 1267-1274.
Zheng YX. Metabolic syndrome and Components and Risk of Breast Cancer in Women Meta-analysis[D]. Tangshan: North China University of Science and Technology, 2023.
Zhou L, Gao H, Zhang J, et al . Metabolic syndrome and cancer risk: a two-sample Mendelian randomization study of European ancestry[J ] . Int J Surg, 2025, 111(1): 311-321.
Zeng C, Liu S, Wei Y, et al . Novel Causal Evidence for the Role of Circulating Lipid Metabolites in Breast Cancer Risk: A Bidirectional Mendelian Randomization Analysis[J ] . J Nutr Metab, 2025, 2025: 2292774.
Loroña NC, Othus M, Malone KE, et al . Metabolic syndrome and risks of breast cancer outcomes for luminal, triple-negative, and HER2-overexpressing subtypes[J ] . Cancer Epidemiol Biomarkers Prev, 2025, 34(1): 117-124.
Tian HY, Shi HP. Hyperlipidemia in cancer patients: defender or killer?[J]. Zhong Liu Dai Xie Yu Ying Yang Dian Zi Za Zhi, 2025, 12(1): 1-6.
Tang DD, Jiang Y, Liu WW, et al. Progress on Epidemiological Studies for the Relationship Between Plasma Glucose Indicators and Breast Cancer Risk[J]. Zhongguo Zhong Liu, 2025, 34(1): 67-72.
Su H. A Study of the Metabolic Syndrome and Its Components in Relation to Invasive Breast Cancer in Women[D]. Tangshan: North China University of Science and Technology, 2024.
Jin H, Shi MX, Yu XX, et al. Prognostic value of the ratio of triglyceride to prealbumin in breast cancer[J]. Lin Chuang Jun Yi Za Zhi, 2023, 51(6): 574-578.
Harborg S, Larsen HB, Elsgaard S, et al . Metabolic syndrome is associated with breast cancer mortality: A systematic review and meta-analysis[J ] . J Intern Med, 2025, 297(3): 262-275.
Karra P, Winn M, Pauleck S, et al . Metabolic dysfunction and obesity-related cancer: Beyond obesity and metabolic syndrome[J ] . Obesity (Silver Spring), 2022, 30(7): 1323-1334.
Yin J, Tang WF, Shao AZ, et al . Caspase8 rs1035142 GT polymorphism was associated with an increased risk of esophageal cancer in a Chinese population[J ] . Mol Biol Rep, 2014, 41(4): 2037-2043.
Chen ZT. Identification of genes related to the genetic susceptibility of breast cancer based on transcriptome-wide association studies and multi-omics analyses[D]. Guangzhou: Southern Medical University, 2025.
Han MS, Ma HC, Hu X, et al. Screening of molecular markers in breast cancer based on GEO database[J]. Zhongguo Zhong Liu Sheng Wu Zhi Liao Za Zhi, 2020, 27(2): 170-176.
Zhou JH. Casp8 Inhibits PD-L1 Expression: the Mechanism andits Implication in Immunotherapy[D]. Chengdu: Sichuan University, 2021.
Sun RY. α-KG causes pyroptosis in cancer cell through Caspase-8[D]. Xiamen: Xiamen University, 2021.
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