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dc.contributor.authorWatts, Eleanor L.
dc.contributor.authorPerez-Cornago, Aurora
dc.contributor.authorFensom, Georgina K.
dc.contributor.authorSmith-Byrne, Karl
dc.contributor.authorNoor, Urwah
dc.contributor.authorAndrews, Colm D.
dc.contributor.authorGunter, Marc J.
dc.contributor.authorHolmes, Michael V.
dc.contributor.authorMartin, Richard M.
dc.contributor.authorTsilidis, Konstantinos K.
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorBarricarte, Aurelio
dc.contributor.authorBueno-de-Mesquita, Bas
dc.contributor.authorChen, Chu
dc.contributor.authorCohn, Barbara A.
dc.contributor.authorDimou, Niki L.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorFlicker, Leon
dc.contributor.authorFreedman, Neal D.
dc.contributor.authorGiles, Graham G.
dc.contributor.authorGiovannucci, Edward L.
dc.contributor.authorGoodman, Gary E.
dc.contributor.authorHaiman, Christopher A.
dc.contributor.authorHankey, Graeme J.
dc.contributor.authorHuang, Jiaqi
dc.contributor.authorHuang, Wen-Yi
dc.contributor.authorHurwitz, Lauren M.
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKnekt, Paul
dc.contributor.authorKubo, Tatsuhiko
dc.contributor.authorLangseth, Hilde
dc.contributor.authorLaughlin, Gail
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorLuostarinen, Tapio
dc.contributor.authorMacInnis, Robert J.
dc.contributor.authorMäenpää, Hanna O.
dc.contributor.authorMännistö, Satu
dc.contributor.authorMetter, E. Jeffrey
dc.contributor.authorMikami, Kazuya
dc.contributor.authorMucci, Lorelei A.
dc.contributor.authorOlsen, Anja
dc.contributor.authorOzasa, Kotaro
dc.contributor.authorPalli, Domenico
dc.contributor.authorPenney, Kathryn L.
dc.contributor.authorPlatz, Elizabeth A.
dc.contributor.authorRissanen, Harri
dc.contributor.authorSawada, Norie
dc.contributor.authorSchenk, Jeannette M.
dc.contributor.authorStattin, Pär
dc.contributor.authorTamakoshi, Akiko
dc.contributor.authorThysell, Elin
dc.contributor.authorTsai, Chiaojung Jillian
dc.contributor.authorTsugane, Shoichiro
dc.contributor.authorVatten, Lars Johan
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorWeinstein, Stephanie J.
dc.contributor.authorWilkens, Lynne R.
dc.contributor.authorYeap, Bu B.
dc.contributor.authorAllen, Naomi E.
dc.contributor.authorKey, Timothy J.
dc.contributor.authorTravis, Ruth C.
dc.description.abstractPrevious studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; P<sub>het</sub> = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.en_US
dc.identifier.citationWatts, Perez-Cornago, Fensom, Smith-Byrne, Noor, Andrews, Gunter, Holmes, Martin, Tsilidis, Albanes, Barricarte, Bueno-de-Mesquita, Chen, Cohn, Dimou, Ferrucci, Flicker, Freedman, Giles, Giovannucci, Goodman, Haiman, Hankey, Huang, Huang, Hurwitz, Kaaks, Knekt, Kubo, Langseth, Laughlin, Le Marchand, Luostarinen, MacInnis, Mäenpää, Männistö, Metter, Mikami, Mucci, Olsen, Ozasa, Palli, Penney, Platz, Rissanen, Sawada, Schenk, Stattin, Tamakoshi, Thysell, Tsai, Tsugane, Vatten, Weiderpass, Weinstein, Wilkens, Yeap, Allen, Key, Travis. Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia. International Journal of Cancer. 2022;151(7):1033-1046en_US
dc.identifier.cristinIDFRIDAID 2057687
dc.relation.journalInternational Journal of Cancer
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleCirculating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortiaen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)