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A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer

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Abstract

Background

Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population.

Methods

The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed.

Results

The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level.

Conclusion

Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.

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Data availability statement

Data is presented in the manuscript and in the supplementary file. Any other raw data will also be provided on question from editorial staff.

Abbreviations

BPA:

Bisphenol A

EDC:

Endocrine-disrupting chemical

DCIS:

Ductal carcinoma in situ

IDC:

Invasive ductal carcinoma

SOD:

Superoxide dismutase

CAT:

Catalase

ROS:

Reactive oxygen species

ZEB1:

Zinc finger E-box binding protein 1

EMT:

Epithelial to mesenchymal transition

EPA:

Environmental protection agency

WWF:

World Wide Fund for nature

HPLC:

High-performance liquid chromatography

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Acknowledgements

Faculty of Biological Sciences Quaid-i-Azam University Islamabad, Higher Education Commission (HEC) Pakistan.

Funding

This work was supported by Higher Education Commission of Pakistan and Quaid-i-Azam University, URF (University research fund) to Dr. Iram Murtaza.

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Authors and Affiliations

  1. Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan

    Ayesha Ishtiaq & Iram Murtaza

  2. Rawalpindi Medical University, Rawalpindi, Pakistan

    Jahangir Sarwar Khan & Sara Malik

  3. Department of Biochemistry, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan

    Maryam Anyat Nasrullah, Usman Tareen, Mariam Anees & Aneesa Sultan

Authors
  1. Ayesha Ishtiaq
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  2. Maryam Anyat Nasrullah
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  4. Sara Malik
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  5. Usman Tareen
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  6. Mariam Anees
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  7. Aneesa Sultan
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  8. Iram Murtaza
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Contributions

Ayesha Ishtiaq (AI), Maryam Anayat Nasrullah (MAN), Jahangir Sarwar Khan (JSK), Sara Malik (SM), Usman Tareen (UT), Mariam Anees (MA), Aneesa Sultan (AS), Iram Murtaza (IM). AI, MAN, AS, and IM were involved in the conception and design of the study. AI, MAN, JSK, SM, UT, MA, AS, and IM were involved in the data execution and interpretation. AI, MAN, JSK, SM, UT, MA, AS, IM were involved in the investigation and methodology. AI, MAN, JSK, SM, UT, MA, AS, and IM were involved in the writing original draft writing. IM was involved in the funding acquisition, supervision, validation, review, and editing.

Corresponding authors

Correspondence to Ayesha Ishtiaq, Aneesa Sultan or Iram Murtaza.

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All authors declare no conflict of interest.

Ethical approval

All the experimental work was performed according to the guidelines of National Institute of Health, Islamabad after the Ethical approval from the Institutional Review Board of Quaid-i-Azam University, Islamabad.

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Ishtiaq, A., Nasrullah, M.A., Khan, J.S. et al. A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer. J Cancer Res Clin Oncol 149, 14565–14575 (2023). https://doi.org/10.1007/s00432-023-05247-3

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