{"doi":"10.1093/jncics/pkab091","title":"Circulating Insulin-Like Growth Factor 1–Related Biomarkers and Risk of Lethal Prostate Cancer","abstract":"Abstract Background Experimental and epidemiologic evidence supports the role of circulating insulin-like growth factor-1 (IGF-1) levels with the risk of prostate cancer. Most circulating IGF-1 is bound to specific binding proteins, and only about 5% circulates in a free form. We explored the relation of free IGF-1 and other components of the IGF system with lethal prostate cancer. Methods Using prospectively collected samples, we undertook a nested case-only analysis among 434 men with lethal prostate cancer and 524 men with indolent, nonlethal prostate cancer in the Physicians’ Health Study and the Health Professionals Follow-up Study. Prediagnostic plasma samples were assayed for free IGF-1 and total IGF-1, acid labile subunit, pregnancy-associated plasma protein A (PAPP-A), and intact and total IGF binding protein 4. We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the associations between IGF-1–related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index. Results Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer (pooled adjusted OR = 1.42, 95% CI = 1.04 to 1.92) compared with men in the lowest 3 quartiles. There were no statistically significant differences in the other plasma analytes. The positive association between PAPP-A and lethal prostate cancer was present among men with intact PTEN but not among those with tumor PTEN loss (2-sided Pinteraction = .001). Conclusions Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease.","journal":"JNCI Cancer Spectrum","year":2021,"id":180907,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":731061,"name":"Ye Wang","orcid":"0000-0002-3133-3348","position":1,"is_corresponding":false},{"id":352539,"name":"Kathryn M. Wilson","orcid":"0000-0003-3106-3971","position":2,"is_corresponding":false},{"id":104569,"name":"Lorelei A. Mucci","orcid":"0000-0002-2551-4927","position":3,"is_corresponding":false},{"id":55362,"name":"Meir J. Stampfer","orcid":"0000-0001-8865-935X","position":4,"is_corresponding":false},{"id":451658,"name":"Michaël Pollak","orcid":"0000-0003-3047-0604","position":5,"is_corresponding":false},{"id":23874,"name":"Kathryn L. Penney","orcid":"0000-0002-2815-3450","position":6,"is_corresponding":false},{"id":363225,"name":"Chaoran Ma","orcid":"0000-0003-3683-3218","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:48:01.257885Z","pmid":"35047751","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":[]}