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

Biomarkers, Tumor / genetics Breast / cytology Breast Neoplasms / genetics Cervix Uteri / cytology CpG Islands DNA Methylation Epigenome Epigenomics / methods Epithelial Cells / metabolism Female Humans Mutation Prognosis ROC Curve

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 02 2022
Historique:
received: 20 05 2021
accepted: 02 12 2021
entrez: 2 2 2022
pubmed: 3 2 2022
medline: 15 2 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-021-27918-w PMID: 35105882 PMC: PMC8807602
pubmed: 35105882
doi: 10.1038/s41467-021-27918-w
pii: 10.1038/s41467-021-27918-w
pmc: PMC8807602
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Evaluation Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

449

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

James E Barrett (JE)

European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria.
Department of Women's Cancer, University College London, London, UK.
Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.

Chiara Herzog (C)

European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria.
Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
ORCID: 0000-0002-1572-498X

Allison Jones (A)

Department of Women's Cancer, University College London, London, UK.

Olivia C Leavy (OC)

Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
ORCID: 0000-0002-1503-5535

Iona Evans (I)

Department of Women's Cancer, University College London, London, UK.

Susanne Knapp (S)

Department of Women's Cancer, University College London, London, UK.

Daniel Reisel (D)

Department of Women's Cancer, University College London, London, UK.

Tatiana Nazarenko (T)

Department of Women's Cancer, University College London, London, UK.
ORCID: 0000-0002-4245-7346

Yoo-Na Kim (YN)

European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria.
Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
ORCID: 0000-0002-0202-3228

Dorella Franchi (D)

Istituto Europeo di Oncologia, IRCCS, Milan, Italy.

Andy Ryan (A)

Department of Women's Cancer, University College London, London, UK.

Joanna Franks (J)

Breast Service, University College London Hospital, London, UK.

Line Bjørge (L)

Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.

Michal Zikan (M)

Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University in Prague, University Hospital Bulovka, Prague, Czech Republic.
ORCID: 0000-0001-5266-8895

David Cibula (D)

Gynaecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, Prague, Czech Republic.
ORCID: 0000-0001-6387-9356

Nadia Harbeck (N)

Breast Center, Department of Obstetrics and Gynecology, University of Munich (LMU), Munich, Germany.
ORCID: 0000-0002-9744-7372

Nicoletta Colombo (N)

Istituto Europeo di Oncologia, IRCCS, Milan, Italy.
University of Milano-Bicocca, Milan, Italy.

Frank Dudbridge (F)

Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
ORCID: 0000-0002-8817-8908

Louise Jones (L)

Centre for Tumour Biology Department, Barts Cancer Institute, Queen Mary University of London, London, UK.

Karin Sundström (K)

Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.

Joakim Dillner (J)

Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0001-8588-6506

Angelique Flöter Rådestad (AF)

Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Kristina Gemzell-Danielsson (K)

Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
ORCID: 0000-0001-6516-1444

Nora Pashayan (N)

Department of Applied Health Research, University College London, London, UK.
ORCID: 0000-0003-0843-2468

Martin Widschwendter (M)

European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria. martin.widschwendter@uibk.ac.at.
Department of Women's Cancer, University College London, London, UK. martin.widschwendter@uibk.ac.at.
Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria. martin.widschwendter@uibk.ac.at.
Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. martin.widschwendter@uibk.ac.at.
ORCID: 0000-0002-7778-8380

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Régions du corps › Région mammaire › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Appareil urogénital › Système génital › Système génital de la femme › Utérus › Col de l'utérus › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Cellules › Cellules épithéliales › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Diagnostic › Pronostic › The WID-BC-index identifies women with primary...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Courbe ROC › The WID-BC-index identifies women with primary...