The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects
Cadmium (Cd), an endocrine disruptor, has been linked to hormone-related cancers, including breast cancer (BC). However, previous studies investigating the association between Cd exposure and BC risk have yielded inconsistent results, and the effects of Cd on BC subtypes remain poorly understood. We...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325005834 |
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| author | Yongbin Lu Yongxia Dang Yilin Chen Yizhuo Chen Xu Hui Xiaonan Li Xin Fan Jingru Yang Xiaoling Ling Li Ma Zhiyuan Cheng Kehu Yang |
| author_facet | Yongbin Lu Yongxia Dang Yilin Chen Yizhuo Chen Xu Hui Xiaonan Li Xin Fan Jingru Yang Xiaoling Ling Li Ma Zhiyuan Cheng Kehu Yang |
| author_sort | Yongbin Lu |
| collection | DOAJ |
| description | Cadmium (Cd), an endocrine disruptor, has been linked to hormone-related cancers, including breast cancer (BC). However, previous studies investigating the association between Cd exposure and BC risk have yielded inconsistent results, and the effects of Cd on BC subtypes remain poorly understood. We employed logistic regression and restricted cubic splines (RCS) to examine the relationship between Cd exposure and BC. A meta-analysis was subsequently conducted to validate the association between Cd exposure and BC. Lastly, mediation analysis was applied to explore the underlying mechanisms linking Cd exposure to BC. Data from 5954 participants in the National Health and Nutrition Examination Survey (1999–2020) were analyzed. Elevated Cd levels in the fourth quartile were significantly associated with an increased BC risk (odds ratio (OR) = 3.74, 95 % confidence interval (CI): 1.45 - 9.62, Ptrend = 0.019), compared to the first quartile group. A linear dose-response relationship was seen between urinary Cd levels and BC risk (Pnon-linear = 0.532), with BC risk increasing 317 % (OR = 3.17, 95 % CI: 1.93 - 5.20, Ptrend < 0.001) for 1 μg/g creatinine increases in urinary Cd levels. The meta-analysis, which included 20 eligible studies, further observed a possible link between Cd exposure and BC risk (relative risk (RR) = 1.17, 95 % CI: 1.06 - 1.29, I2 = 83 %), particularly in estrogen receptor-positive (ER+) subtypes (RR = 1.08, 95 % CI: 1.01 - 1.16, I2 = 70 %). Mediation analysis further revealed that glycated hemoglobin (HbA1c) mediated 9.09 % of the Cd-BC risk association. In conclusion, the study results suggest a potential association between Cd levels and an increased BC risk, particularly in ER+ subtypes. Mechanistically, HbA1c was identified as a mediator in this association. These findings underscore the complex interplay between Cd exposure and metabolic dysregulation in the development of BC, highlighting the potential role of HbA1c in modulating BC risk among individuals exposed to Cd. |
| format | Article |
| id | doaj-art-9ff140ea8d8f4fa3a28467b0e48a579f |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-9ff140ea8d8f4fa3a28467b0e48a579f2025-08-20T01:51:04ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129711824710.1016/j.ecoenv.2025.118247The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effectsYongbin Lu0Yongxia Dang1Yilin Chen2Yizhuo Chen3Xu Hui4Xiaonan Li5Xin Fan6Jingru Yang7Xiaoling Ling8Li Ma9Zhiyuan Cheng10Kehu Yang11Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Social Science Research Center, Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe Second Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaEvidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Social Science Research Center, Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Occupational and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; Correspondence to: School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China.School of Public Health, Sun Yat-sen University, Guangzhou, China; Correspondence to: School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Social Science Research Center, Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou, Gansu, China; Correspondence to: School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, China.Cadmium (Cd), an endocrine disruptor, has been linked to hormone-related cancers, including breast cancer (BC). However, previous studies investigating the association between Cd exposure and BC risk have yielded inconsistent results, and the effects of Cd on BC subtypes remain poorly understood. We employed logistic regression and restricted cubic splines (RCS) to examine the relationship between Cd exposure and BC. A meta-analysis was subsequently conducted to validate the association between Cd exposure and BC. Lastly, mediation analysis was applied to explore the underlying mechanisms linking Cd exposure to BC. Data from 5954 participants in the National Health and Nutrition Examination Survey (1999–2020) were analyzed. Elevated Cd levels in the fourth quartile were significantly associated with an increased BC risk (odds ratio (OR) = 3.74, 95 % confidence interval (CI): 1.45 - 9.62, Ptrend = 0.019), compared to the first quartile group. A linear dose-response relationship was seen between urinary Cd levels and BC risk (Pnon-linear = 0.532), with BC risk increasing 317 % (OR = 3.17, 95 % CI: 1.93 - 5.20, Ptrend < 0.001) for 1 μg/g creatinine increases in urinary Cd levels. The meta-analysis, which included 20 eligible studies, further observed a possible link between Cd exposure and BC risk (relative risk (RR) = 1.17, 95 % CI: 1.06 - 1.29, I2 = 83 %), particularly in estrogen receptor-positive (ER+) subtypes (RR = 1.08, 95 % CI: 1.01 - 1.16, I2 = 70 %). Mediation analysis further revealed that glycated hemoglobin (HbA1c) mediated 9.09 % of the Cd-BC risk association. In conclusion, the study results suggest a potential association between Cd levels and an increased BC risk, particularly in ER+ subtypes. Mechanistically, HbA1c was identified as a mediator in this association. These findings underscore the complex interplay between Cd exposure and metabolic dysregulation in the development of BC, highlighting the potential role of HbA1c in modulating BC risk among individuals exposed to Cd.http://www.sciencedirect.com/science/article/pii/S0147651325005834CadmiumBreast cancerHbA1cMediating effects |
| spellingShingle | Yongbin Lu Yongxia Dang Yilin Chen Yizhuo Chen Xu Hui Xiaonan Li Xin Fan Jingru Yang Xiaoling Ling Li Ma Zhiyuan Cheng Kehu Yang The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects Ecotoxicology and Environmental Safety Cadmium Breast cancer HbA1c Mediating effects |
| title | The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects |
| title_full | The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects |
| title_fullStr | The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects |
| title_full_unstemmed | The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects |
| title_short | The impact of cadmium exposure on breast cancer risk: Exploring dose-response relationships and mediating effects |
| title_sort | impact of cadmium exposure on breast cancer risk exploring dose response relationships and mediating effects |
| topic | Cadmium Breast cancer HbA1c Mediating effects |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325005834 |
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