{"doi":"10.3390/metabo14080463","title":"Metabolite Predictors of Breast and Colorectal Cancer Risk in the Women’s Health Initiative","abstract":"Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women’s Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development.","journal":"Metabolites","year":2024,"id":447356,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9163,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275665,"name":"Brian D. Williamson","orcid":"0000-0002-7024-548X","position":1,"is_corresponding":false},{"id":394416,"name":"Ying Huang","orcid":"0000-0002-9655-7502","position":2,"is_corresponding":false},{"id":327990,"name":"G. A. Nagana Gowda","orcid":"0000-0002-0544-7464","position":3,"is_corresponding":false},{"id":304577,"name":"Daniel Raftery","orcid":"0000-0003-2467-8118","position":4,"is_corresponding":false},{"id":342795,"name":"Lesley F. Tinker","orcid":"0000-0003-2469-1929","position":5,"is_corresponding":false},{"id":625721,"name":"Cheng Zheng","orcid":"0000-0002-6562-870X","position":6,"is_corresponding":false},{"id":420900,"name":"Shirley A.A. Beresford","orcid":"0000-0002-1631-3541","position":7,"is_corresponding":false},{"id":949875,"name":"Hayley Purcell","orcid":null,"position":8,"is_corresponding":false},{"id":304576,"name":"Danijel Djukovic","orcid":"0000-0001-5954-8810","position":9,"is_corresponding":false},{"id":331095,"name":"Haiwei Gu","orcid":"0000-0002-7598-5022","position":10,"is_corresponding":false},{"id":858026,"name":"Howard D. Strickler","orcid":"0000-0001-6397-7466","position":11,"is_corresponding":false},{"id":230958,"name":"Fred K. Tabung","orcid":"0000-0001-8193-7150","position":12,"is_corresponding":false},{"id":243126,"name":"Ross L. Prentice","orcid":"0000-0003-2849-5757","position":13,"is_corresponding":false},{"id":27761,"name":"Marian L. Neuhouser","orcid":"0000-0002-3876-0000","position":14,"is_corresponding":false},{"id":252206,"name":"Johanna W. Lampe","orcid":"0000-0003-2717-3780","position":15,"is_corresponding":false},{"id":342261,"name":"Sandi L. Navarro","orcid":"0000-0002-4260-2486","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:59.101070Z","pmid":"39195559","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":[]}