Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations
Abstract Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 m...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-021-00226-8 |
| _version_ | 1797427284833992704 |
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| author | Neil M. Iyengar Xi Kathy Zhou Hillary Mendieta Omar El-Hely Dilip D. Giri Lisle Winston Domenick J. Falcone Hanhan Wang Lingsong Meng Taehoon Ha Michael Pollak Monica Morrow Andrew J. Dannenberg |
| author_facet | Neil M. Iyengar Xi Kathy Zhou Hillary Mendieta Omar El-Hely Dilip D. Giri Lisle Winston Domenick J. Falcone Hanhan Wang Lingsong Meng Taehoon Ha Michael Pollak Monica Morrow Andrew J. Dannenberg |
| author_sort | Neil M. Iyengar |
| collection | DOAJ |
| description | Abstract Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline BRCA1 (n = 74) or BRCA2 (n = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals (P < 0.05). Obesity was associated with breast white adipose tissue inflammation, which correlated with breast aromatase levels (P < 0.01). Circulating C-reactive protein, interleukin-6, and leptin positively correlated with body mass index and breast aromatase levels, whereas negative correlations were observed for adiponectin and sex hormone-binding globulin (P < 0.05). These findings could help explain the increased risk of early-onset breast cancer in obese BRCA1/2 mutation carriers. |
| first_indexed | 2024-03-09T08:42:05Z |
| format | Article |
| id | doaj.art-9bc77085a3d541aca6d6d81c076de591 |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T08:42:05Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-9bc77085a3d541aca6d6d81c076de5912023-12-02T16:32:43ZengNature Portfolionpj Breast Cancer2374-46772021-03-01711710.1038/s41523-021-00226-8Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutationsNeil M. Iyengar0Xi Kathy Zhou1Hillary Mendieta2Omar El-Hely3Dilip D. Giri4Lisle Winston5Domenick J. Falcone6Hanhan Wang7Lingsong Meng8Taehoon Ha9Michael Pollak10Monica Morrow11Andrew J. Dannenberg12Departments of Medicine, Memorial Sloan Kettering Cancer CenterDepartments of Population Health Sciences, Weill Cornell Medical CollegeDepartments of Medicine, Memorial Sloan Kettering Cancer CenterDepartments of Medicine, Weill Cornell Medical CollegeDepartments of Pathology, Memorial Sloan Kettering Cancer CenterDepartments of Medicine, Weill Cornell Medical CollegeDepartments of Pathology and Laboratory Medicine, Weill Cornell Medical CollegeDepartments of Population Health Sciences, Weill Cornell Medical CollegeDepartments of Population Health Sciences, Weill Cornell Medical CollegeDepartments of Population Health Sciences, Weill Cornell Medical CollegeDepartments of Medicine and Oncology, McGill UniversityDepartments of Surgery, Memorial Sloan Kettering Cancer CenterDepartments of Medicine, Weill Cornell Medical CollegeAbstract Obesity is associated with an increased risk of breast cancer in post-menopausal women and decreased risk in pre-menopausal women. Conversely, in BRCA1/2 mutation carriers, pre-menopausal obesity is associated with early-onset breast cancer. Here we show that obese, pre-menopausal BRCA1/2 mutation carriers have increased levels of aromatase and inflammation in the breast, as occurs in post-menopausal women. In a prospective cohort study of 141 women with germline BRCA1 (n = 74) or BRCA2 (n = 67) mutations, leptin, and aromatase expression were higher in the breast tissue of obese versus lean individuals (P < 0.05). Obesity was associated with breast white adipose tissue inflammation, which correlated with breast aromatase levels (P < 0.01). Circulating C-reactive protein, interleukin-6, and leptin positively correlated with body mass index and breast aromatase levels, whereas negative correlations were observed for adiponectin and sex hormone-binding globulin (P < 0.05). These findings could help explain the increased risk of early-onset breast cancer in obese BRCA1/2 mutation carriers.https://doi.org/10.1038/s41523-021-00226-8 |
| spellingShingle | Neil M. Iyengar Xi Kathy Zhou Hillary Mendieta Omar El-Hely Dilip D. Giri Lisle Winston Domenick J. Falcone Hanhan Wang Lingsong Meng Taehoon Ha Michael Pollak Monica Morrow Andrew J. Dannenberg Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations npj Breast Cancer |
| title | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations |
| title_full | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations |
| title_fullStr | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations |
| title_full_unstemmed | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations |
| title_short | Effects of obesity on breast aromatase expression and systemic metabo-inflammation in women with BRCA1 or BRCA2 mutations |
| title_sort | effects of obesity on breast aromatase expression and systemic metabo inflammation in women with brca1 or brca2 mutations |
| url | https://doi.org/10.1038/s41523-021-00226-8 |
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