{"doi":"10.1093/jnci/djaa169","title":"Early-Life Body Adiposity and the Breast Tumor Transcriptome","abstract":"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 < 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). CONCLUSIONS: These findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association.","journal":"JNCI Journal of the National Cancer Institute","year":2020,"id":79812,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8854,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329365,"name":"Cheng Peng","orcid":"0000-0002-0220-5128","position":1,"is_corresponding":false},{"id":415061,"name":"Catherine Guranich","orcid":null,"position":2,"is_corresponding":false},{"id":363597,"name":"Yujing J. Heng","orcid":"0000-0002-8930-817X","position":3,"is_corresponding":false},{"id":363595,"name":"Gabrielle M. Baker","orcid":"0000-0002-9213-0317","position":4,"is_corresponding":false},{"id":415062,"name":"Christopher A. Rubadue","orcid":null,"position":5,"is_corresponding":false},{"id":36157,"name":"Kimberly Glass","orcid":"0000-0003-4394-5779","position":6,"is_corresponding":false},{"id":104571,"name":"A. Heather Eliassen","orcid":"0000-0002-3961-6609","position":7,"is_corresponding":false},{"id":321496,"name":"Rulla M. Tamimi","orcid":"0000-0003-2306-8668","position":8,"is_corresponding":false},{"id":414226,"name":"Kornélia Polyák","orcid":"0000-0002-5964-0382","position":9,"is_corresponding":false},{"id":305538,"name":"Susan E. Hankinson","orcid":"0000-0001-9155-3767","position":10,"is_corresponding":false},{"id":414225,"name":"Jun Wang","orcid":"0000-0001-8372-1863","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T21:50:57.971597Z","pmid":"33136151","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}