Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study
Current research on the relationship between environmental endocrine disrupting chemicals (EDCs) and breast cancer remains insufficient, with limited evidence and inconsistent conclusions. Mendelian randomization (MR) is a robust method for establishing causality, as it reduces biases from confoundi...
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Elsevier
2025-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325001277 |
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| author | Ningning Song Xinquan Xi Kuan Yang Chongzhe Pei Lingzhou Zhao |
| author_facet | Ningning Song Xinquan Xi Kuan Yang Chongzhe Pei Lingzhou Zhao |
| author_sort | Ningning Song |
| collection | DOAJ |
| description | Current research on the relationship between environmental endocrine disrupting chemicals (EDCs) and breast cancer remains insufficient, with limited evidence and inconsistent conclusions. Mendelian randomization (MR) is a robust method for establishing causality, as it reduces biases from confounding factors and reverse causation. This study uses MR to investigate the effects of three types of EDCs, including bisphenols, parabens, and phthalates, on the risk of overall breast cancer and its subtypes—Luminal A, Luminal B, triple negative, human epidermal growth factor receptor 2-enriched, and estrogen receptor-positive/negative. The study also examines the 1400 blood metabolome as potential mediators and explores EDCs-associated DNA methylation changes as potential factors, with a focus on European populations. Our results shows that n-butyl paraben (n-BuP) is positively associated with Luminal A, mono-methyl phthalate is negatively associated with Luminal B, and mono-iso-butyl phthalate (MiBP) is positively associated with triple negative breast cancer (TNBC). Mediation analysis reveals that blood metabolites, such as caffeic acid sulfate and the caffeine-to-paraxanthine ratio, mediate the effect of n-BuP on Luminal A, while methylsuccinate mediate the effect of MiBP on TNBC. Epigenetic analysis shows associations between EDCs exposure-related DNA methylation changes at specific CpG sites (cg26325335, cg08537847, cg27454300) and different breast cancer risks. These findings not only suggest potential biomarkers for early detection and intervention but also underscore the imperative for further research to rigorously validate these associations. |
| format | Article |
| id | doaj-art-17808c309d694afb9a0470a30e8dd27b |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-17808c309d694afb9a0470a30e8dd27b2025-02-04T04:10:16ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-01291117791Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization studyNingning Song0Xinquan Xi1Kuan Yang2Chongzhe Pei3Lingzhou Zhao4Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui 230022, PR ChinaDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui 230022, PR ChinaDepartment of Cardiology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping, Tianjin 300052, PR China; Corresponding authors.Department of Cardiology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping, Tianjin 300052, PR China; Corresponding authors.Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China; Corresponding authors.Current research on the relationship between environmental endocrine disrupting chemicals (EDCs) and breast cancer remains insufficient, with limited evidence and inconsistent conclusions. Mendelian randomization (MR) is a robust method for establishing causality, as it reduces biases from confounding factors and reverse causation. This study uses MR to investigate the effects of three types of EDCs, including bisphenols, parabens, and phthalates, on the risk of overall breast cancer and its subtypes—Luminal A, Luminal B, triple negative, human epidermal growth factor receptor 2-enriched, and estrogen receptor-positive/negative. The study also examines the 1400 blood metabolome as potential mediators and explores EDCs-associated DNA methylation changes as potential factors, with a focus on European populations. Our results shows that n-butyl paraben (n-BuP) is positively associated with Luminal A, mono-methyl phthalate is negatively associated with Luminal B, and mono-iso-butyl phthalate (MiBP) is positively associated with triple negative breast cancer (TNBC). Mediation analysis reveals that blood metabolites, such as caffeic acid sulfate and the caffeine-to-paraxanthine ratio, mediate the effect of n-BuP on Luminal A, while methylsuccinate mediate the effect of MiBP on TNBC. Epigenetic analysis shows associations between EDCs exposure-related DNA methylation changes at specific CpG sites (cg26325335, cg08537847, cg27454300) and different breast cancer risks. These findings not only suggest potential biomarkers for early detection and intervention but also underscore the imperative for further research to rigorously validate these associations.http://www.sciencedirect.com/science/article/pii/S0147651325001277EDCsBlood MetabolomeEpigeneticsBreast cancerMendelian Randomization |
| spellingShingle | Ningning Song Xinquan Xi Kuan Yang Chongzhe Pei Lingzhou Zhao Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study Ecotoxicology and Environmental Safety EDCs Blood Metabolome Epigenetics Breast cancer Mendelian Randomization |
| title | Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study |
| title_full | Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study |
| title_fullStr | Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study |
| title_full_unstemmed | Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study |
| title_short | Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study |
| title_sort | effects of endocrine disrupting chemicals blood metabolome and epigenetics on breast cancer risk a multi dimensional mendelian randomization study |
| topic | EDCs Blood Metabolome Epigenetics Breast cancer Mendelian Randomization |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325001277 |
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