ArticleJournal of the National Cancer Institute2021
Early-Life Body Adiposity and the Breast Tumor Transcriptome.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis.Breast cancer research : BCR · 2024Pooled it
- Visceral adiposity and breast cancer outcomes: transcriptomic analysis of the tumor microenvironment by intrinsic subtype.Breast cancer research : BCR · 2026Article
- Associations of early-adulthood adiposity with breast parenchymal tissue complexity within premenopausal women.Breast cancer research : BCR · 2025Article
- The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause.Carcinogenesis · 2025Article
- Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers.International journal of molecular sciences · 2024Article
- Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.Scientific reports · 2023Article
- Epidemiology and Risk Factors for Breast Cancer: 21st Century Advances, Gaps to Address through Interdisciplinary Science.Cold Spring Harbor perspectives in medicine · 2023Review
- Oncobiology and treatment of breast cancer in young women.Cancer metastasis reviews · 2022Review
- Understanding Adiposity at Different Times Across the Life Course and Cancer Risk: Is Evidence Sufficient to Act?Journal of the National Cancer Institute · 2022Article
- Refining the Focus on Early Life and Adolescent Pathways to Prevent Breast Cancer.Journal of the National Cancer Institute · 2021Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundCumulative 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.
methodsWe 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).
resultsNo 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 < 0.05) upregulated or downregulated gene sets. In stratified analyses by tumor ER status, larger body size during ages 10-20 years was associated with decreased cellular proliferation pathways, including MYC target genes, in both ER+ and ER- tumors. In ER+ tumors, larger body size was also associated with upregulation in genes involved in TNFα/NFkB signaling. In ER- tumors, larger body size was additionally associated with downregulation in genes involved in interferon α and interferon γ immune response and Phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling; the INFγ response pathway was also downregulated in ER- tumor-adjacent tissue, though at borderline statistical significance (false discovery rate = 0.1).
conclusionsThese findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association.
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