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000179958 041__ $$aEnglish
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000179958 1001_ $$00000-0001-9229-2589$$aWatts, Eleanor L$$b0
000179958 245__ $$aCirculating free testosterone and risk of aggressive prostate cancer: prospective and Mendelian randomization analyses in international consortia.
000179958 260__ $$aBognor Regis$$bWiley-Liss$$c2022
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000179958 500__ $$a2022 Oct 1;151(7):1033-1046
000179958 520__ $$aPrevious 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 1,870 aggressive prostate cancers). In Mendelian randomization (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; Phet =0.0003: 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.
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000179958 7001_ $$00000-0002-5652-356X$$aPerez-Cornago, Aurora$$b1
000179958 7001_ $$aFensom, Georgina K$$b2
000179958 7001_ $$aSmith-Byrne, Karl$$b3
000179958 7001_ $$aNoor, Urwah$$b4
000179958 7001_ $$aAndrews, Colm D$$b5
000179958 7001_ $$aGunter, Marc J$$b6
000179958 7001_ $$aHolmes, Michael V$$b7
000179958 7001_ $$aMartin, Richard M$$b8
000179958 7001_ $$00000-0002-8452-8472$$aTsilidis, Konstantinos K$$b9
000179958 7001_ $$aAlbanes, Demetrius$$b10
000179958 7001_ $$aBarricarte, Aurelio$$b11
000179958 7001_ $$aBueno-de-Mesquita, H Bas$$b12
000179958 7001_ $$aChen, Chu$$b13
000179958 7001_ $$aCohn, Barbara A$$b14
000179958 7001_ $$00000-0003-1678-9328$$aDimou, Niki L$$b15
000179958 7001_ $$aFerrucci, Luigi$$b16
000179958 7001_ $$aFlicker, Leon$$b17
000179958 7001_ $$aFreedman, Neal D$$b18
000179958 7001_ $$aGiles, Graham G$$b19
000179958 7001_ $$aGiovannucci, Edward L$$b20
000179958 7001_ $$aGoodman, Gary E$$b21
000179958 7001_ $$aHaiman, Christopher A$$b22
000179958 7001_ $$aHankey, Graeme J$$b23
000179958 7001_ $$00000-0002-7808-9477$$aHuang, Jiaqi$$b24
000179958 7001_ $$aHuang, Wen-Yi$$b25
000179958 7001_ $$00000-0001-8932-5028$$aHurwitz, Lauren M$$b26
000179958 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b27$$udkfz
000179958 7001_ $$aKnekt, Paul$$b28
000179958 7001_ $$aKubo, Tatsuhiko$$b29
000179958 7001_ $$aLangseth, Hilde$$b30
000179958 7001_ $$aLaughlin, Gail$$b31
000179958 7001_ $$aLe Marchand, Loic$$b32
000179958 7001_ $$00000-0003-3231-8550$$aLuostarinen, Tapio$$b33
000179958 7001_ $$aMacInnis, Robert J$$b34
000179958 7001_ $$aMäenpää, Hanna O$$b35
000179958 7001_ $$aMännistö, Satu$$b36
000179958 7001_ $$aMetter, E Jeffrey$$b37
000179958 7001_ $$aMikami, Kazuya$$b38
000179958 7001_ $$aMucci, Lorelei A$$b39
000179958 7001_ $$aOlsen, Anja W$$b40
000179958 7001_ $$aOzasa, Kotaro$$b41
000179958 7001_ $$00000-0002-5558-2437$$aPalli, Domenico$$b42
000179958 7001_ $$aPenney, Kathryn L$$b43
000179958 7001_ $$00000-0003-3676-8954$$aPlatz, Elizabeth A$$b44
000179958 7001_ $$aRissanen, Harri$$b45
000179958 7001_ $$00000-0002-9936-1476$$aSawada, Norie$$b46
000179958 7001_ $$aSchenk, Jeannette M$$b47
000179958 7001_ $$aStattin, Pär$$b48
000179958 7001_ $$aTamakoshi, Akiko$$b49
000179958 7001_ $$aThysell, Elin$$b50
000179958 7001_ $$aTsai, Chiaojung Jillian$$b51
000179958 7001_ $$aTsugane, Shoichiro$$b52
000179958 7001_ $$aVatten, Lars$$b53
000179958 7001_ $$00000-0003-2237-0128$$aWeiderpass, Elisabete$$b54
000179958 7001_ $$aWeinstein, Stephanie J$$b55
000179958 7001_ $$aWilkens, Lynne R$$b56
000179958 7001_ $$aYeap, Bu B$$b57
000179958 7001_ $$aPRACTICAL consortium, CRUK, BPC, CAPS, PEGASUS$$b58$$eCollaboration Author
000179958 7001_ $$aAllen, Naomi E$$b59
000179958 7001_ $$aKey, Timothy J$$b60
000179958 7001_ $$aTravis, Ruth C$$b61
000179958 7001_ $$aEeles, Rosalind A$$b62
000179958 7001_ $$aHaiman, Christopher A$$b63
000179958 7001_ $$aKote-Jarai, Zsofia$$b64
000179958 7001_ $$aSchumacher, Fredrick R$$b65
000179958 7001_ $$aBenlloch, Sara$$b66
000179958 7001_ $$aOlama, Ali Amin Al$$b67
000179958 7001_ $$aMuir, Kenneth R$$b68
000179958 7001_ $$aBerndt, Sonja I$$b69
000179958 7001_ $$aConti, David V$$b70
000179958 7001_ $$aWiklund, Fredrik$$b71
000179958 7001_ $$aChanock, Stephen$$b72
000179958 7001_ $$aWang, Ying$$b73
000179958 7001_ $$aTangen, Catherine M$$b74
000179958 7001_ $$aBatra, Jyotsna$$b75
000179958 7001_ $$aClements, Judith A$$b76
000179958 7001_ $$aBioResource, Apcb$$b77
000179958 7001_ $$aGrönberg, Henrik$$b78
000179958 7001_ $$aPashayan, Nora$$b79
000179958 7001_ $$aSchleutker, Johanna$$b80
000179958 7001_ $$aAlbanes, Demetrius$$b81
000179958 7001_ $$aWeinstein, Stephanie$$b82
000179958 7001_ $$aWolk, Alicja$$b83
000179958 7001_ $$aWest, Catharine M L$$b84
000179958 7001_ $$aMucci, Lorelei A$$b85
000179958 7001_ $$aCancel-Tassin, Géraldine$$b86
000179958 7001_ $$aKoutros, Stella$$b87
000179958 7001_ $$aSørensen, Karina Dalsgaard$$b88
000179958 7001_ $$aGrindedal, Eli Marie$$b89
000179958 7001_ $$aNeal, David E$$b90
000179958 7001_ $$aHamdy, Freddie C$$b91
000179958 7001_ $$aDonovan, Jenny L$$b92
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000179958 7001_ $$aMenegaux, Florence$$b125
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