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Obesity-associated changes in molecular biology of primary breast cancer

Author

Listed:
  • Ha-Linh Nguyen

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Tatjana Geukens

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Marion Maetens

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Samuel Aparicio

    (BC Cancer Research Centre
    University of British Columbia)

  • Ayse Bassez

    (Department of Human Genetics
    VIB Center for Cancer Biology)

  • Ake Borg

    (Lund University
    Lund University Cancer Center Lund
    Lund University
    Lund University)

  • Jane Brock

    (Brigham and Women’s Hospital)

  • Annegien Broeks

    (Antoni van Leeuwenhoek, the Netherlands Cancer Institute)

  • Carlos Caldas

    (Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge)

  • Fatima Cardoso

    (Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation)

  • Maxim Schepper

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Mauro Delorenzi

    (University of Lausanne
    SIB Swiss Institute of Bioinformatics, Bioinformatics Core Facility)

  • Caroline A. Drukker

    (Department of Surgical Oncology, Antoni van Leeuwenhoek Hospital)

  • Annuska M. Glas

    (Agendia)

  • Andrew R. Green

    (University of Nottingham)

  • Edoardo Isnaldi

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Jórunn Eyfjörð

    (University of Iceland)

  • Hazem Khout

    (University Hospitals of Leicester NHS Trust)

  • Stian Knappskog

    (University of Bergen
    Haukeland University Hospital)

  • Savitri Krishnamurthy

    (The University of Texas MD Anderson Cancer Center)

  • Sunil R. Lakhani

    (The University of Queensland
    The Royal Brisbane and Women’s Hospital)

  • Anita Langerod

    (Oslo University Hospital)

  • John W. M. Martens

    (Erasmus University Medical Center)

  • Amy E. McCart Reed

    (The University of Queensland)

  • Leigh Murphy

    (University of Manitoba and Cancer Care Manitoba Research Institute)

  • Stefan Naulaerts

    (Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine)

  • Serena Nik-Zainal

    (University of Cambridge
    University of Cambridge)

  • Ines Nevelsteen

    (University Hospitals Leuven)

  • Patrick Neven

    (University Hospitals Leuven)

  • Martine Piccart

    (Institut Jules Bordet and Université Libre de Bruxelles)

  • Coralie Poncet

    (European Organisation for Research and Treatment of Cancer (EORTC) Headquarters)

  • Kevin Punie

    (Leuven Cancer Institute and University Hospitals Leuven)

  • Colin Purdie

    (University of Dundee, NHS Tayside)

  • Emad A. Rakha

    (University of Nottingham
    Nottingham University Hospital NHS Trust, City Hospital Campus)

  • Andrea Richardson

    (Johns Hopkins University School of Medicine)

  • Emiel Rutgers

    (Netherlands Cancer Institute)

  • Anne Vincent-Salomon

    (PSL Research University)

  • Peter T. Simpson

    (The University of Queensland)

  • Marjanka K. Schmidt

    (Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital)

  • Christos Sotiriou

    (Institut Jules Bordet, Universite Libre de Bruxelles)

  • Paul N. Span

    (Radboud University Medical Center)

  • Kiat Tee Benita Tan

    (Sengkang General Hospital
    Singapore General Hospital
    National Cancer Centre)

  • Alastair Thompson

    (Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine)

  • Stefania Tommasi

    (Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumouri “Giovanni Paolo II”)

  • Karen Baelen

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Marc Vijver

    (Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam)

  • Steven Laere

    (Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp)

  • Laura van’t Veer

    (UCSF Helen Diller Family Comprehensive Cancer Center)

  • Giuseppe Viale

    (IEO, European Institute of Oncology IRCCS
    University of Milan)

  • Alain Viari

    (Synergie Lyon Cancer, Plateforme de Bio-informatique ‘Gilles Thomas’)

  • Hanne Vos

    (University Hospitals Leuven)

  • Anke T. Witteveen

    (Agendia)

  • Hans Wildiers

    (Leuven Cancer Institute and University Hospitals Leuven)

  • Giuseppe Floris

    (University Hospitals Leuven)

  • Abhishek D. Garg

    (Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine)

  • Ann Smeets

    (University Hospitals Leuven)

  • Diether Lambrechts

    (Department of Human Genetics
    VIB Center for Cancer Biology)

  • Elia Biganzoli

    (Università degli Studi di Milano)

  • François Richard

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Christine Desmedt

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

Abstract

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.

Suggested Citation

  • Ha-Linh Nguyen & Tatjana Geukens & Marion Maetens & Samuel Aparicio & Ayse Bassez & Ake Borg & Jane Brock & Annegien Broeks & Carlos Caldas & Fatima Cardoso & Maxim Schepper & Mauro Delorenzi & Caroli, 2023. "Obesity-associated changes in molecular biology of primary breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39996-z
    DOI: 10.1038/s41467-023-39996-z
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    References listed on IDEAS

    as
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    2. Serena Nik-Zainal & Helen Davies & Johan Staaf & Manasa Ramakrishna & Dominik Glodzik & Xueqing Zou & Inigo Martincorena & Ludmil B. Alexandrov & Sancha Martin & David C. Wedge & Peter Van Loo & Young, 2016. "Landscape of somatic mutations in 560 breast cancer whole-genome sequences," Nature, Nature, vol. 534(7605), pages 47-54, June.
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