Evidence map›Paper›PMID 42437780›Full record

ArticleImmunogenetics2026

Causal relationship and pathogenic mechanism analysis of breast cancer and coronary heart disease based on mendelian randomization and transcriptome data analysis.

Mingbin Xie, Yuanhong Wu, Xinyao Jin, Fengchun Jiang, Qiang Yao

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Article in Immunogenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

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5 authors.

Mingbin XieDepartment of Cardiology, Hangzhou Red Cross Hospital, No.208 East Huancheng Road, Gongshu District, Hangzhou City, Zhejiang Province, 310003, China. xiemingbin194@126.com.
Yuanhong WuDepartment of Cardiology, Hangzhou Red Cross Hospital, No.208 East Huancheng Road, Gongshu District, Hangzhou City, Zhejiang Province, 310003, China.
Xinyao JinDepartment of Cardiology, Hangzhou Red Cross Hospital, No.208 East Huancheng Road, Gongshu District, Hangzhou City, Zhejiang Province, 310003, China.
Fengchun JiangDepartment of Cardiology, Hangzhou Red Cross Hospital, No.208 East Huancheng Road, Gongshu District, Hangzhou City, Zhejiang Province, 310003, China.
Qiang YaoDepartment of Cardiology, Hangzhou Red Cross Hospital, No.208 East Huancheng Road, Gongshu District, Hangzhou City, Zhejiang Province, 310003, China.

Funding

Zhejiang Chinese Medicine Science and Technology Project 2025ZL097
6 · The paper itself

Abstract

Breast cancer (BC) is closely linked to coronary heart disease (CHD), yet the genetic causal relationship and common driving mechanism between the two have not been fully elucidated. The purpose of this study is to infer the causal relationship between BC and CHD at the genetic level and identify the cross-omic molecular characteristics of them through the integrated analysis of multiple genomics. Firstly, large-scale Genome Wide Association Study (GWAS) data were used for bidirectional Mendelian randomization (MR) analysis. Secondly, multi-center transcriptome data were integrated and combined with differential expression analysis (DEGs) and weighted gene co-expression network analysis (WGCNA) to screen for key comorbidity genes. Univariate, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses were used to construct a prognostic model. The Benjamin Hochberg method was used for False Discovery Rate (FDR) correction. Finally, molecular pathways were explored through Gene Set Enrichment Analysis (GSEA), and key genes were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in independent clinical samples. MR analysis revealed a significant positive correlation between BC and CHD in Asian populations (OR = 1.095, 95% CI: 1.005-1.192, P = 0.037). However, no significant association was observed in European populations. Transcriptome analysis identified a prognostic risk score composed of 5 CHD-related genes (HES1, MLPH, TRIB3, HSPBP1, and STARD3), which can independently predict the prognosis of BC patients. GSEA analysis indicated that the comorbidity mechanism involved dysregulation of cell cycle, immune inflammation, and metabolism-related pathways. qRT-PCR verification confirmed that compared with patients with BC, the expression levels of HES1, TRIB3, HSPBP1, and STARD3 in the peripheral blood of BC combined with CHD patients were significantly upregulated (P < 0.05). This study established for the first time the genetic causal relationship between BC and CHD in Asian populations, and revealed the inflammation-immune-metabolism molecular axis mediating comorbidities. The identified key genes not only serve as biomarkers for BC prognosis, but also provide a new perspective for understanding the pathological mechanisms and precise diagnosis and treatment of tumor cardiovascular comorbidities.

Indexed as

Breast NeoplasmsCoronary DiseaseTranscriptomeFemaleGene Expression ProfilingGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotidePrognosisBreast cancerCoronary heart diseaseMendelian randomizationTranscriptome

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.