Causal Inference on Association Between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization Study

DU Yi; XUE Mengyao; CHEN Huiying; SUN Ying; LUO Tianyu; SUN Haidong

doi:10.3971/j.issn.1000-8578.2026.25.0696

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Causal Inference on Association Between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization Study

更新时间：2026-11-05

- Causal Inference on Association Between Metabolic Syndrome and Breast Cancer: A Bidirectional Two-Sample Mendelian Randomization Study
- Vol. 53, Issue 4, Pages: 267-273(2026)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.3971/j.issn.1000-8578.2026.25.0696
  CLC： R737.9
- Published：2026
- 稿件说明：
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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.

摘要

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（

=1.00，95%

: 0.97~1.03，

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。

Abstract

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 (

=1.00

95%

: 0.97-1.03)

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.

关键词

Keywords

references

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