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Genetic architecture of mammographic density as a risk factor for breast cancer: a systematic review

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Abstract

Background

Mammography Density (MD) is a potential risk marker that is influenced by genetic polymorphisms and can subsequently modulate the risk of breast cancer. This qualitative systematic review summarizes the genes and biological pathways involved in breast density and discusses the potential clinical implications in view of the genetic risk profile for breast density.

Methods

The terms related to “Common genetic variations” and “Breast density” were searched in Scopus, PubMed, and Web of Science databases. Gene pathways analysis and assessment of protein interactions were also performed.

Results

Eighty-six studies including 111 genes, reported a significant association between mammographic density in different populations. ESR1, IGF1, IGFBP3, and ZNF365 were the most prevalent genes. Moreover, estrogen metabolism, signal transduction, and prolactin signaling pathways were significantly related to the associated genes. Mammography density was an associated phenotype, and eight out of 111 genes, including COMT, CYP19A1, CYP1B1, ESR1, IGF1, IGFBP1, IGFBP3, and LSP1, were modifiers of this trait.

Conclusion

Genes involved in developmental processes and the evolution of secondary sexual traits play an important role in determining mammographic density. Due to the effect of breast tissue density on the risk of breast cancer, these genes may also be associated with breast cancer risk.

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  1. Asma Khorshid Shamshiri and Maryam Alidoust have contributed equal to this work.

Authors and Affiliations

  1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Asma Khorshid Shamshiri, Maryam Alidoust, Mahboubeh Hemmati Nokandei & Alireza Pasdar

  2. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Asma Khorshid Shamshiri, Maryam Alidoust & Mahboubeh Hemmati Nokandei

  3. Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

    Alireza Pasdar

  4. Clinical Research Development Unit, Faculty of Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, 917794-8564, Iran

    Fahimeh Afzaljavan

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Design the research: AKS, Data collection: AKS, MA and MH, Statistical analysis: AKS, and MA, Manuscript draft: AKS, MA, FA, and AP. All authors helped edit and approve the final version of this manuscript for submission. They also participated in the finalization of manuscript and approved the final draft.

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Khorshid Shamshiri, A., Alidoust, M., Hemmati Nokandei, M. et al. Genetic architecture of mammographic density as a risk factor for breast cancer: a systematic review. Clin Transl Oncol 25, 1729–1747 (2023). https://doi.org/10.1007/s12094-022-03071-8

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