A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development

Abstract Breast cancer is the most common cancer among women worldwide. The present study utilized a bidirectional Mendelian randomization methodology to explore the causal associations between 35 blood and urinary metabolic markers and distinct subtypes of breast cancer. The MR-PRESSO method was em...

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Main Authors: Ting Lin, Yimin Liu, Zixuan Liu, Ao Liu, Runtong Liu, Qianchao Wang
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02461-y
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author Ting Lin
Yimin Liu
Zixuan Liu
Ao Liu
Runtong Liu
Qianchao Wang
author_facet Ting Lin
Yimin Liu
Zixuan Liu
Ao Liu
Runtong Liu
Qianchao Wang
author_sort Ting Lin
collection DOAJ
description Abstract Breast cancer is the most common cancer among women worldwide. The present study utilized a bidirectional Mendelian randomization methodology to explore the causal associations between 35 blood and urinary metabolic markers and distinct subtypes of breast cancer. The MR-PRESSO method was employed to detect and correct for pleiotropic effects, with statistical significance adjusted using the false discovery rate (FDR). The findings revealed significant causal links between certain metabolic markers and specific breast cancer subtypes. Specifically, glucose (OR: −0.187; 95% CI: −0.344 to −0.030) and glycated hemoglobin (HbA1c) (OR: −0.150; 95% CI: −0.2498 to −0.051) were associated with benign breast cancer. In contrast, statin-adjusted apolipoprotein B (OR: 0.493; 95% CI: 0.029 to 0.957) and low-density lipoprotein (LDL) (OR: 0.550; 95% CI: 0.056 to 1.043), urinary sodium (OR: −3.138; 95% CI: −5.710 to −0.565), and triglycerides (OR: 0.606; 95% CI: 0.0824 to 1.129) were correlated with intraductal carcinoma in situ. Apolipoprotein A (OR: 0.178; 95% CI: 0.053 to 0.304) and high-density lipoprotein (HDL) cholesterol (OR: 0.159; 95% CI: 0.045 to 0.273) were linked to intraductal carcinoma in situ of the breast, while total protein (OR: 0.800; 95% CI: 0.181 to 1.409) and albumin (OR: 0.883; 95% CI: 0.255 to 1.512) were associated with lobular carcinoma in situ. In the reverse analysis, benign breast cancer (OR: 0.014; 95% CI: 0.002 to 0.026) exhibited a correlation with urinary creatinine, and intraductal carcinoma in situ (OR: 0.004; 95% CI: 0.001 to 0.007) with insulin-like growth factor 1 (IGF-1). This study identifies key biomarkers for breast cancer susceptibility and resistance, offering a scientific foundation for further research endeavors.
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spelling doaj-art-85c15d980d93461aaf4e2b0e436895402025-08-20T01:47:29ZengSpringerDiscover Oncology2730-60112025-05-0116111310.1007/s12672-025-02461-yA Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer developmentTing Lin0Yimin Liu1Zixuan Liu2Ao Liu3Runtong Liu4Qianchao Wang5Department of Breast Surgery, Tangshan People’s HospitalNorth China University of Science and TechnologyNorth China University of Science and TechnologyDongfang College, Beijing University of Traditional Chinese MedicineNorth China University of Science and TechnologyDepartment of Thoracic Surgery, Tangshan People’s HospitalAbstract Breast cancer is the most common cancer among women worldwide. The present study utilized a bidirectional Mendelian randomization methodology to explore the causal associations between 35 blood and urinary metabolic markers and distinct subtypes of breast cancer. The MR-PRESSO method was employed to detect and correct for pleiotropic effects, with statistical significance adjusted using the false discovery rate (FDR). The findings revealed significant causal links between certain metabolic markers and specific breast cancer subtypes. Specifically, glucose (OR: −0.187; 95% CI: −0.344 to −0.030) and glycated hemoglobin (HbA1c) (OR: −0.150; 95% CI: −0.2498 to −0.051) were associated with benign breast cancer. In contrast, statin-adjusted apolipoprotein B (OR: 0.493; 95% CI: 0.029 to 0.957) and low-density lipoprotein (LDL) (OR: 0.550; 95% CI: 0.056 to 1.043), urinary sodium (OR: −3.138; 95% CI: −5.710 to −0.565), and triglycerides (OR: 0.606; 95% CI: 0.0824 to 1.129) were correlated with intraductal carcinoma in situ. Apolipoprotein A (OR: 0.178; 95% CI: 0.053 to 0.304) and high-density lipoprotein (HDL) cholesterol (OR: 0.159; 95% CI: 0.045 to 0.273) were linked to intraductal carcinoma in situ of the breast, while total protein (OR: 0.800; 95% CI: 0.181 to 1.409) and albumin (OR: 0.883; 95% CI: 0.255 to 1.512) were associated with lobular carcinoma in situ. In the reverse analysis, benign breast cancer (OR: 0.014; 95% CI: 0.002 to 0.026) exhibited a correlation with urinary creatinine, and intraductal carcinoma in situ (OR: 0.004; 95% CI: 0.001 to 0.007) with insulin-like growth factor 1 (IGF-1). This study identifies key biomarkers for breast cancer susceptibility and resistance, offering a scientific foundation for further research endeavors.https://doi.org/10.1007/s12672-025-02461-yBlood and urine biomarkersBreast cancerMendelian randomization
spellingShingle Ting Lin
Yimin Liu
Zixuan Liu
Ao Liu
Runtong Liu
Qianchao Wang
A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
Discover Oncology
Blood and urine biomarkers
Breast cancer
Mendelian randomization
title A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
title_full A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
title_fullStr A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
title_full_unstemmed A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
title_short A Mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
title_sort mendelian randomization study investigating the causal associations of 35 blood and urinary metabolite biomarkers with breast cancer development
topic Blood and urine biomarkers
Breast cancer
Mendelian randomization
url https://doi.org/10.1007/s12672-025-02461-y
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