Obesity-associated changes in molecular biology of primary breast cancer
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Published:2023-07-21
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Nguyen Ha-LinhORCID, Geukens Tatjana, Maetens Marion, Aparicio SamuelORCID, Bassez Ayse, Borg AkeORCID, Brock Jane, Broeks Annegien, Caldas CarlosORCID, Cardoso FatimaORCID, De Schepper MaximORCID, Delorenzi Mauro, Drukker Caroline A., Glas Annuska M.ORCID, Green Andrew R.ORCID, Isnaldi EdoardoORCID, Eyfjörð Jórunn, Khout Hazem, Knappskog StianORCID, Krishnamurthy Savitri, Lakhani Sunil R.ORCID, Langerod Anita, Martens John W. M.ORCID, McCart Reed Amy E.ORCID, Murphy Leigh, Naulaerts StefanORCID, Nik-Zainal SerenaORCID, Nevelsteen Ines, Neven Patrick, Piccart MartineORCID, Poncet Coralie, Punie Kevin, Purdie ColinORCID, Rakha Emad A., Richardson Andrea, Rutgers Emiel, Vincent-Salomon AnneORCID, Simpson Peter T.ORCID, Schmidt Marjanka K.ORCID, Sotiriou ChristosORCID, Span Paul N.ORCID, Tan Kiat Tee Benita, Thompson Alastair, Tommasi StefaniaORCID, Van Baelen Karen, Van de Vijver Marc, Van Laere Steven, van’t Veer LauraORCID, Viale Giuseppe, Viari Alain, Vos HanneORCID, Witteveen Anke T., Wildiers HansORCID, Floris GiuseppeORCID, Garg Abhishek D.ORCID, Smeets AnnORCID, Lambrechts DietherORCID, Biganzoli EliaORCID, Richard FrançoisORCID, Desmedt ChristineORCID
Abstract
AbstractObesity 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference79 articles.
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