Early-Life Body Adiposity and the Breast Tumor Transcriptome
| Autor: | Jun Wang, A. Heather Eliassen, Christopher A. Rubadue, Susan E. Hankinson, Kornelia Polyak, Catherine Guranich, Yujing J. Heng, Cheng Peng, Gabrielle M. Baker, Rulla M. Tamimi, Kimberly Glass |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Cancer Research Adolescent Estrogen receptor Breast Neoplasms Biology Transcriptome 03 medical and health sciences Phosphatidylinositol 3-Kinases Young Adult 0302 clinical medicine Breast cancer Downregulation and upregulation medicine Humans Obesity Child Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Adiposity 0303 health sciences Articles Hyperplasia medicine.disease Oncology 030220 oncology & carcinogenesis Cancer research Tumor necrosis factor alpha Female |
| Zdroj: | J Natl Cancer Inst |
| ISSN: | 1460-2105 |
| Popis: | Background Cumulative epidemiologic evidence has shown that early-life adiposity is strongly inversely associated with breast cancer risk throughout life, independent of adult obesity. However, the molecular mechanisms remain poorly understood. Methods We assessed the association of early-life adiposity, defined as self-reported body size during ages 10-20 years from a validated 9-level pictogram, with the transcriptome of breast tumor (N = 835) and tumor-adjacent histologically normal tissue (N = 663) in the Nurses’ Health Study. We conducted multivariable linear regression analysis to identify differentially expressed genes in tumor and tumor-adjacent tissue, respectively. Molecular pathway analysis using Hallmark gene sets (N = 50) was further performed to gain biological insights. Analysis was stratified by tumor estrogen receptor (ER) protein expression status (n = 673 for ER+ and 162 for ER− tumors). Results No gene was statistically significantly differentially expressed by early-life body size after multiple comparison adjustment. However, pathway analysis revealed several statistically significantly (false discovery rate Conclusions These findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association. |
| Databáze: | OpenAIRE |
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