{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:22:28Z","timestamp":1788481348592,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"US Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-18-1-0158 to MS"],"award-info":[{"award-number":["W81XWH-18-1-0158 to MS"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01CA167552"],"award-info":[{"award-number":["U01CA167552"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2019 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\u2013related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jncics\/pkab091","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T20:23:38Z","timestamp":1639081418000},"source":"Crossref","is-referenced-by-count":14,"title":["Circulating Insulin-Like Growth Factor 1\u2013Related Biomarkers and Risk of Lethal Prostate Cancer"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-3218","authenticated-orcid":false,"given":"Chaoran","family":"Ma","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-3348","authenticated-orcid":false,"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"Oncology Department, McGill University and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2551-4927","authenticated-orcid":false,"given":"Lorelei A","family":"Mucci","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meir J","family":"Stampfer","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pollak","sequence":"additional","affiliation":[{"name":"Oncology Department, McGill University and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2815-3450","authenticated-orcid":false,"given":"Kathryn L","family":"Penney","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. 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