Obesity increases DNA damage in the breast epithelium
Abstract Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue. In a m...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-025-01961-7 |
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| author | Mohamed Gaber Arnaud Quentel Julia Holmes Cassandra Lepetit Hana Triki Adam Wilson Valerie Payne Iliana Tenvooren Cloé Dehours Abigail Peoples Mary L. Duet Adam J. Katz Thierry Pécot Gwenola Bougras-Cartron Pierre-François Cartron Katherine L. Cook Pierre-Alexandre Vidi |
| author_facet | Mohamed Gaber Arnaud Quentel Julia Holmes Cassandra Lepetit Hana Triki Adam Wilson Valerie Payne Iliana Tenvooren Cloé Dehours Abigail Peoples Mary L. Duet Adam J. Katz Thierry Pécot Gwenola Bougras-Cartron Pierre-François Cartron Katherine L. Cook Pierre-Alexandre Vidi |
| author_sort | Mohamed Gaber |
| collection | DOAJ |
| description | Abstract Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue. In a mouse model of diet-induced obesity, weight gain was associated with elevated levels of DNA double-strand breaks in the mammary gland. We also found a positive correlation between BMI and DNA breaks in the breast epithelium of premenopausal women (but not postmenopausal women). High BMI was associated with elevated systemic and tissue-level oxidative DNA damage across the lifespan, and we propose that the breast epithelium undergoing menstruous proliferation waves is particularly prone to the generation of DNA breaks from oxidative lesions. Ancestry was an important modulator of the obesity-DNA break connection. Compared to non-Hispanic Whites, women identifying as African Americans had higher levels of DNA breaks, as well as elevated leptin and IGF-1. In 3D cultures of breast acini, both leptin and IGF-1 caused an accumulation of DNA damage. The results highlight a connection between premalignant genomic alterations in the breast epithelium and metabolic health modulated by obesity and ancestry. They call for attention on biological determinants of breast cancer risk disparities. |
| format | Article |
| id | doaj-art-ce31962e807248e78b61146a00690b5f |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-ce31962e807248e78b61146a00690b5f2025-01-26T12:58:50ZengBMCBreast Cancer Research1465-542X2025-01-0127111510.1186/s13058-025-01961-7Obesity increases DNA damage in the breast epitheliumMohamed Gaber0Arnaud Quentel1Julia Holmes2Cassandra Lepetit3Hana Triki4Adam Wilson5Valerie Payne6Iliana Tenvooren7Cloé Dehours8Abigail Peoples9Mary L. Duet10Adam J. Katz11Thierry Pécot12Gwenola Bougras-Cartron13Pierre-François Cartron14Katherine L. Cook15Pierre-Alexandre Vidi16Department of Cancer Biology, Wake Forest University School of MedicineInstitut de Cancérologie de l’OuestDepartment of Cancer Biology, Wake Forest University School of MedicineInstitut de Cancérologie de l’OuestUniversité d’Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICATDepartment of Cancer Biology, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineInstitut de Cancérologie de l’OuestDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of MedicineDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of MedicineDepartment of Plastic and Reconstructive Surgery, Wake Forest University School of MedicineBiosit, UAR 3480 CNRS – US 18 Inserm, Rennes UniversityUniversité d’Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICATUniversité d’Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, SFR ICATDepartment of Cancer Biology, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineAbstract Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue. In a mouse model of diet-induced obesity, weight gain was associated with elevated levels of DNA double-strand breaks in the mammary gland. We also found a positive correlation between BMI and DNA breaks in the breast epithelium of premenopausal women (but not postmenopausal women). High BMI was associated with elevated systemic and tissue-level oxidative DNA damage across the lifespan, and we propose that the breast epithelium undergoing menstruous proliferation waves is particularly prone to the generation of DNA breaks from oxidative lesions. Ancestry was an important modulator of the obesity-DNA break connection. Compared to non-Hispanic Whites, women identifying as African Americans had higher levels of DNA breaks, as well as elevated leptin and IGF-1. In 3D cultures of breast acini, both leptin and IGF-1 caused an accumulation of DNA damage. The results highlight a connection between premalignant genomic alterations in the breast epithelium and metabolic health modulated by obesity and ancestry. They call for attention on biological determinants of breast cancer risk disparities.https://doi.org/10.1186/s13058-025-01961-7Breast cancer riskObesityCancer health disparitiesMolecular markersDNA double-strand breaks3D cell culture |
| spellingShingle | Mohamed Gaber Arnaud Quentel Julia Holmes Cassandra Lepetit Hana Triki Adam Wilson Valerie Payne Iliana Tenvooren Cloé Dehours Abigail Peoples Mary L. Duet Adam J. Katz Thierry Pécot Gwenola Bougras-Cartron Pierre-François Cartron Katherine L. Cook Pierre-Alexandre Vidi Obesity increases DNA damage in the breast epithelium Breast Cancer Research Breast cancer risk Obesity Cancer health disparities Molecular markers DNA double-strand breaks 3D cell culture |
| title | Obesity increases DNA damage in the breast epithelium |
| title_full | Obesity increases DNA damage in the breast epithelium |
| title_fullStr | Obesity increases DNA damage in the breast epithelium |
| title_full_unstemmed | Obesity increases DNA damage in the breast epithelium |
| title_short | Obesity increases DNA damage in the breast epithelium |
| title_sort | obesity increases dna damage in the breast epithelium |
| topic | Breast cancer risk Obesity Cancer health disparities Molecular markers DNA double-strand breaks 3D cell culture |
| url | https://doi.org/10.1186/s13058-025-01961-7 |
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