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The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

Author

Listed:
  • James E. Barrett

    (Universität Innsbruck, Innsbruck
    University College London
    Universität Innsbruck)

  • Chiara Herzog

    (Universität Innsbruck, Innsbruck
    Universität Innsbruck)

  • Allison Jones

    (University College London)

  • Olivia C. Leavy

    (University of Leicester
    London School of Hygiene and Tropical Medicine)

  • Iona Evans

    (University College London)

  • Susanne Knapp

    (University College London)

  • Daniel Reisel

    (University College London)

  • Tatiana Nazarenko

    (University College London)

  • Yoo-Na Kim

    (Universität Innsbruck, Innsbruck
    Universität Innsbruck)

  • Dorella Franchi

    (Istituto Europeo di Oncologia, IRCCS)

  • Andy Ryan

    (University College London)

  • Joanna Franks

    (Breast Service, University College London Hospital)

  • Line Bjørge

    (Haukeland University Hospital
    Department of Clinical Science, University of Bergen)

  • Michal Zikan

    (First Faculty of Medicine, Charles University in Prague, University Hospital Bulovka)

  • David Cibula

    (Charles University in Prague, General University Hospital in Prague)

  • Nadia Harbeck

    (University of Munich (LMU))

  • Nicoletta Colombo

    (Istituto Europeo di Oncologia, IRCCS
    University of Milano-Bicocca)

  • Frank Dudbridge

    (University of Leicester
    London School of Hygiene and Tropical Medicine)

  • Louise Jones

    (Barts Cancer Institute, Queen Mary University of London)

  • Karin Sundström

    (Division of Pathology, Karolinska Institutet)

  • Joakim Dillner

    (Division of Pathology, Karolinska Institutet)

  • Angelique Flöter Rådestad

    (Karolinska Institutet and Karolinska University Hospital)

  • Kristina Gemzell-Danielsson

    (Karolinska Institutet and Karolinska University Hospital)

  • Nora Pashayan

    (University College London)

  • Martin Widschwendter

    (Universität Innsbruck, Innsbruck
    University College London
    Universität Innsbruck
    Karolinska Institutet and Karolinska University Hospital)

Abstract

Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women’s risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80–0.88) and 0.81 (95% CI: 0.76–0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.

Suggested Citation

  • James E. Barrett & Chiara Herzog & Allison Jones & Olivia C. Leavy & Iona Evans & Susanne Knapp & Daniel Reisel & Tatiana Nazarenko & Yoo-Na Kim & Dorella Franchi & Andy Ryan & Joanna Franks & Line Bj, 2022. "The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27918-w
    DOI: 10.1038/s41467-021-27918-w
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