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Obesity-associated changes in molecular biology of primary breast cancer

Nguyen, H.-L. ; Borg, A. LU and Desmedt, C. (2023) In Nature Communications 14(1).
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... (More)
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. © 2023, The Author(s). (Less)
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keywords
Breast Neoplasms, Female, Genomics, Humans, Molecular Biology, Obesity, Overweight, Tumor Microenvironment, estrogen receptor, biology, body mass, cancer, cell component, health risk, obesity, risk factor, tumor, Article, breast cancer, cohort analysis, controlled study, genomics, human, human tissue, inflammation, molecular biology, obese patient, primary tumor, single cell analysis, transcriptomics, tumor microenvironment, breast tumor, complication, female, genetics
in
Nature Communications
volume
14
issue
1
article number
4418
publisher
Nature Publishing Group
external identifiers
  • scopus:85165361124
ISSN
2041-1723
DOI
10.1038/s41467-023-39996-z
language
English
LU publication?
yes
id
5fd14790-c0b9-4949-8f84-7bd55ba8c20f
date added to LUP
2023-11-15 10:58:26
date last changed
2023-11-15 10:59:46
@article{5fd14790-c0b9-4949-8f84-7bd55ba8c20f,
  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. © 2023, The Author(s).}},
  author       = {{Nguyen, H.-L. and Borg, A. and Desmedt, C.}},
  issn         = {{2041-1723}},
  keywords     = {{Breast Neoplasms; Female; Genomics; Humans; Molecular Biology; Obesity; Overweight; Tumor Microenvironment; estrogen receptor; biology; body mass; cancer; cell component; health risk; obesity; risk factor; tumor; Article; breast cancer; cohort analysis; controlled study; genomics; human; human tissue; inflammation; molecular biology; obese patient; primary tumor; single cell analysis; transcriptomics; tumor microenvironment; breast tumor; complication; female; genetics}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Obesity-associated changes in molecular biology of primary breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-39996-z}},
  doi          = {{10.1038/s41467-023-39996-z}},
  volume       = {{14}},
  year         = {{2023}},
}