Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance

Manuel Scimeca; Erica Giacobbi; Rita Bonfiglio; Renata Sisto; Stefano Casciardi; Francesca Servadei; Daniel R S Middleton; Julia Bischof; Maria Paola Scioli; Giorgio Modesti; Eleonora Candi; Gerry Melino; Alessandro Mauriello

doi:10.1038/s41420-025-02676-6

Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance

Manuel Scimeca
, Erica Giacobbi
, Rita Bonfiglio
, Renata Sisto
, Stefano Casciardi
, Francesca Servadei
, Daniel R S Middleton
, Julia Bischof
, Maria Paola Scioli
, Giorgio Modesti
, Eleonora Candi
, Gerry Melino
, Alessandro Mauriello

Centre for Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

Lead (Pb) is increasingly recognized for its potential to alter cellular processes and contribute to cancer development. Although Pb is classified as a probable carcinogen by the IARC, the clinical evidence for its role in breast cancer is inconsistent and limited to epidemiological studies yet. The aim of this study was to investigate the Pb bioaccumulation in human breast cancer tissues by correlating its concentration with specific cancer factors related to carcinogenesis. Biopsy samples from 26 breast cancer patients were collected for molecular investigations (DNA and RNA sequencing), histological analysis, and the assessment of Pb concentration by ICP-MS. Data reported here revealed Pb bioaccumulation in all breast cancer samples, with a significant positive correlation between Pb levels and both Tumoral Mutational Burden and Microsatellite Instability, suggesting an association of Pb with genomic instability in human breast cancer samples. Additionally, Pb was associated with increased expression of cell death-related molecules such as BCL2 and p53. This association allows us to hypothesize a potential involvement of Pb in affecting cell death resistance. Interestingly, Pb concentration showed no correlation to other established prognostic and predictive biomarkers of breast cancer, such as PAM50. Thus, Pb concentration may represent a new independent risk factor for breast cancer development. This study provides new insights into the role of Pb bioaccumulation in breast cancer and suggests that environmental exposure to Pb may contribute to more aggressive tumor behavior through mechanisms involving genomic instability and resistance to apoptosis.

Original language	English
Article number	383
Number of pages	7
Journal	Cell death discovery
Volume	11
DOIs	https://doi.org/10.1038/s41420-025-02676-6
Publication status	Published - 15 Aug 2025

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Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance
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Scimeca, M., Giacobbi, E., Bonfiglio, R., Sisto, R., Casciardi, S., Servadei, F., Middleton, D. R. S., Bischof, J., Scioli, M. P., Modesti, G., Candi, E., Melino, G., & Mauriello, A. (2025). Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance. Cell death discovery, 11, Article 383. https://doi.org/10.1038/s41420-025-02676-6

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title = "Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance",

abstract = "Lead (Pb) is increasingly recognized for its potential to alter cellular processes and contribute to cancer development. Although Pb is classified as a probable carcinogen by the IARC, the clinical evidence for its role in breast cancer is inconsistent and limited to epidemiological studies yet. The aim of this study was to investigate the Pb bioaccumulation in human breast cancer tissues by correlating its concentration with specific cancer factors related to carcinogenesis. Biopsy samples from 26 breast cancer patients were collected for molecular investigations (DNA and RNA sequencing), histological analysis, and the assessment of Pb concentration by ICP-MS. Data reported here revealed Pb bioaccumulation in all breast cancer samples, with a significant positive correlation between Pb levels and both Tumoral Mutational Burden and Microsatellite Instability, suggesting an association of Pb with genomic instability in human breast cancer samples. Additionally, Pb was associated with increased expression of cell death-related molecules such as BCL2 and p53. This association allows us to hypothesize a potential involvement of Pb in affecting cell death resistance. Interestingly, Pb concentration showed no correlation to other established prognostic and predictive biomarkers of breast cancer, such as PAM50. Thus, Pb concentration may represent a new independent risk factor for breast cancer development. This study provides new insights into the role of Pb bioaccumulation in breast cancer and suggests that environmental exposure to Pb may contribute to more aggressive tumor behavior through mechanisms involving genomic instability and resistance to apoptosis. ",

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AU - Scimeca, Manuel

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AU - Bonfiglio, Rita

AU - Sisto, Renata

AU - Casciardi, Stefano

AU - Servadei, Francesca

AU - Middleton, Daniel R S

AU - Bischof, Julia

AU - Scioli, Maria Paola

AU - Modesti, Giorgio

AU - Candi, Eleonora

AU - Melino, Gerry

AU - Mauriello, Alessandro

PY - 2025/8/15

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N2 - Lead (Pb) is increasingly recognized for its potential to alter cellular processes and contribute to cancer development. Although Pb is classified as a probable carcinogen by the IARC, the clinical evidence for its role in breast cancer is inconsistent and limited to epidemiological studies yet. The aim of this study was to investigate the Pb bioaccumulation in human breast cancer tissues by correlating its concentration with specific cancer factors related to carcinogenesis. Biopsy samples from 26 breast cancer patients were collected for molecular investigations (DNA and RNA sequencing), histological analysis, and the assessment of Pb concentration by ICP-MS. Data reported here revealed Pb bioaccumulation in all breast cancer samples, with a significant positive correlation between Pb levels and both Tumoral Mutational Burden and Microsatellite Instability, suggesting an association of Pb with genomic instability in human breast cancer samples. Additionally, Pb was associated with increased expression of cell death-related molecules such as BCL2 and p53. This association allows us to hypothesize a potential involvement of Pb in affecting cell death resistance. Interestingly, Pb concentration showed no correlation to other established prognostic and predictive biomarkers of breast cancer, such as PAM50. Thus, Pb concentration may represent a new independent risk factor for breast cancer development. This study provides new insights into the role of Pb bioaccumulation in breast cancer and suggests that environmental exposure to Pb may contribute to more aggressive tumor behavior through mechanisms involving genomic instability and resistance to apoptosis.

AB - Lead (Pb) is increasingly recognized for its potential to alter cellular processes and contribute to cancer development. Although Pb is classified as a probable carcinogen by the IARC, the clinical evidence for its role in breast cancer is inconsistent and limited to epidemiological studies yet. The aim of this study was to investigate the Pb bioaccumulation in human breast cancer tissues by correlating its concentration with specific cancer factors related to carcinogenesis. Biopsy samples from 26 breast cancer patients were collected for molecular investigations (DNA and RNA sequencing), histological analysis, and the assessment of Pb concentration by ICP-MS. Data reported here revealed Pb bioaccumulation in all breast cancer samples, with a significant positive correlation between Pb levels and both Tumoral Mutational Burden and Microsatellite Instability, suggesting an association of Pb with genomic instability in human breast cancer samples. Additionally, Pb was associated with increased expression of cell death-related molecules such as BCL2 and p53. This association allows us to hypothesize a potential involvement of Pb in affecting cell death resistance. Interestingly, Pb concentration showed no correlation to other established prognostic and predictive biomarkers of breast cancer, such as PAM50. Thus, Pb concentration may represent a new independent risk factor for breast cancer development. This study provides new insights into the role of Pb bioaccumulation in breast cancer and suggests that environmental exposure to Pb may contribute to more aggressive tumor behavior through mechanisms involving genomic instability and resistance to apoptosis.

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VL - 11

JO - Cell death discovery

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M1 - 383

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Lead bioaccumulation in human breast cancer tissue is associated with DNA instability and cell death resistance

Abstract

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