Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study

Abstract Background Air pollution has been implicated in various health conditions, including cancer. However, the relationship between long-term exposure to air pollution and breast cancer risk, its subtypes, and survival remains unclear. Methods This study employed a two-sample Mendelian Randomiza...

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Main Authors: Wenhuan Li, Yonggang Yang, Rong Xie, Xinyu Su, Pengfei Shi, Lin Chen, Bo Hu
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02874-9
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author Wenhuan Li
Yonggang Yang
Rong Xie
Xinyu Su
Pengfei Shi
Lin Chen
Bo Hu
author_facet Wenhuan Li
Yonggang Yang
Rong Xie
Xinyu Su
Pengfei Shi
Lin Chen
Bo Hu
author_sort Wenhuan Li
collection DOAJ
description Abstract Background Air pollution has been implicated in various health conditions, including cancer. However, the relationship between long-term exposure to air pollution and breast cancer risk, its subtypes, and survival remains unclear. Methods This study employed a two-sample Mendelian Randomization (MR) design to investigate the causal effects of PM2.5, PM10, NO₂, and NOx on breast cancer risk and survival. Genetic instruments for air pollutants were obtained from the UK Biobank, while breast cancer outcomes, were sourced from the Breast Cancer Association Consortium (BCAC) and the FinnGen study. The primary method was inverse-variance weighted (IVW), MR estimates for outcomes from various datasets were synthesized using the fixed-effects meta-analysis method. Pleiotropy and heterogeneity were evaluated with MR-Egger intercept and Cochran’s Q test, while leave-one-out analysis tested the robustness of the findings. Results MR analysis demonstrated a significant causal association between genetically predicted NO₂ and PM10 exposure and increased breast cancer risk. A one standard deviation (SD) increase in NO₂ was associated with a 68% higher risk of breast cancer, while a one SD increase in PM10 was linked to a 36% increased risk. Subgroup analysis revealed similar associations, particularly for both ER + and ER − subtypes with PM10. In contrast, no significant associations were observed for PM2.5 or NOx. Additionally, no strong evidence was found linking air pollution exposure to breast cancer survival. Conclusions This study provides evidence of a causal link between long-term exposure to NO₂ and PM10 and breast cancer risk, especially for hormone receptor subtypes. However, the effects of PM2.5 and NOx on breast cancer risk were not significant, and air pollution exposure did not appear to impact survival. Further research is needed to elucidate the specific biological mechanisms and to extend the analysis to non-European populations.
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spelling doaj-art-93e6bc7888974bae9ee0ce4daaa774802025-08-20T03:10:32ZengSpringerDiscover Oncology2730-60112025-06-0116111210.1007/s12672-025-02874-9Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization studyWenhuan Li0Yonggang Yang1Rong Xie2Xinyu Su3Pengfei Shi4Lin Chen5Bo Hu6Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Air pollution has been implicated in various health conditions, including cancer. However, the relationship between long-term exposure to air pollution and breast cancer risk, its subtypes, and survival remains unclear. Methods This study employed a two-sample Mendelian Randomization (MR) design to investigate the causal effects of PM2.5, PM10, NO₂, and NOx on breast cancer risk and survival. Genetic instruments for air pollutants were obtained from the UK Biobank, while breast cancer outcomes, were sourced from the Breast Cancer Association Consortium (BCAC) and the FinnGen study. The primary method was inverse-variance weighted (IVW), MR estimates for outcomes from various datasets were synthesized using the fixed-effects meta-analysis method. Pleiotropy and heterogeneity were evaluated with MR-Egger intercept and Cochran’s Q test, while leave-one-out analysis tested the robustness of the findings. Results MR analysis demonstrated a significant causal association between genetically predicted NO₂ and PM10 exposure and increased breast cancer risk. A one standard deviation (SD) increase in NO₂ was associated with a 68% higher risk of breast cancer, while a one SD increase in PM10 was linked to a 36% increased risk. Subgroup analysis revealed similar associations, particularly for both ER + and ER − subtypes with PM10. In contrast, no significant associations were observed for PM2.5 or NOx. Additionally, no strong evidence was found linking air pollution exposure to breast cancer survival. Conclusions This study provides evidence of a causal link between long-term exposure to NO₂ and PM10 and breast cancer risk, especially for hormone receptor subtypes. However, the effects of PM2.5 and NOx on breast cancer risk were not significant, and air pollution exposure did not appear to impact survival. Further research is needed to elucidate the specific biological mechanisms and to extend the analysis to non-European populations.https://doi.org/10.1007/s12672-025-02874-9Air pollutionBreast cancerSurvivalMendelian randomizationCausal relationship
spellingShingle Wenhuan Li
Yonggang Yang
Rong Xie
Xinyu Su
Pengfei Shi
Lin Chen
Bo Hu
Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
Discover Oncology
Air pollution
Breast cancer
Survival
Mendelian randomization
Causal relationship
title Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
title_full Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
title_fullStr Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
title_full_unstemmed Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
title_short Causal associations between air pollution and breast cancer risk and survival: a Mendelian randomization study
title_sort causal associations between air pollution and breast cancer risk and survival a mendelian randomization study
topic Air pollution
Breast cancer
Survival
Mendelian randomization
Causal relationship
url https://doi.org/10.1007/s12672-025-02874-9
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