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@article{Watts:2022:10.1002/ijc.34116,
author = {Watts, EL and Perez-Cornago, A and Fensom, GK and Smith-Byrne, K and Noor, U and Andrews, CD and Gunter, MJ and Holmes, M and Martin, RM and Tsilidis, KK and Albanes, D and Barricarte, A and Bueno-de-Mesquita, B and Chen, C and Cohn, BA and Dimou, NL and Ferrucci, L and Flicker, L and Freedman, ND and Giles, GG and Giovannucci, EL and Goodman, GE and Haiman, CA and Hankey, GJ and Huang, J and Huang, W-Y and Hurwitz, LM and Kaaks, R and Knekt, P and Kubo, T and Langseth, H and Laughlin, G and Le, Marchand L and Luostarinen, T and MacInnis, RJ and Maenpaa, HO and Mannisto, S and Metter, JE and Mikami, K and Mucci, LA and Olsen, AW and Ozasa, K and Palli, D and Penney, KL and Platz, EA and Rissanen, H and Sawada, N and Schenk, JM and Stattin, P and Tamakoshi, A and Thysell, E and Tsai, CJ and Tsugane, S and Vatten, L and Weiderpass, E and Weinstein, SJ and Wilkens, LR and Yeap, BB and Allen, NE and Key, TJ and Travis, RC},
doi = {10.1002/ijc.34116},
journal = {International Journal of Cancer},
pages = {1033--1046},
title = {Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia},
url = {http://dx.doi.org/10.1002/ijc.34116},
volume = {151},
year = {2022}
}

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TY  - JOUR
AB  - Previous 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; Phet = .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.
AU  - Watts,EL
AU  - Perez-Cornago,A
AU  - Fensom,GK
AU  - Smith-Byrne,K
AU  - Noor,U
AU  - Andrews,CD
AU  - Gunter,MJ
AU  - Holmes,M
AU  - Martin,RM
AU  - Tsilidis,KK
AU  - Albanes,D
AU  - Barricarte,A
AU  - Bueno-de-Mesquita,B
AU  - Chen,C
AU  - Cohn,BA
AU  - Dimou,NL
AU  - Ferrucci,L
AU  - Flicker,L
AU  - Freedman,ND
AU  - Giles,GG
AU  - Giovannucci,EL
AU  - Goodman,GE
AU  - Haiman,CA
AU  - Hankey,GJ
AU  - Huang,J
AU  - Huang,W-Y
AU  - Hurwitz,LM
AU  - Kaaks,R
AU  - Knekt,P
AU  - Kubo,T
AU  - Langseth,H
AU  - Laughlin,G
AU  - Le,Marchand L
AU  - Luostarinen,T
AU  - MacInnis,RJ
AU  - Maenpaa,HO
AU  - Mannisto,S
AU  - Metter,JE
AU  - Mikami,K
AU  - Mucci,LA
AU  - Olsen,AW
AU  - Ozasa,K
AU  - Palli,D
AU  - Penney,KL
AU  - Platz,EA
AU  - Rissanen,H
AU  - Sawada,N
AU  - Schenk,JM
AU  - Stattin,P
AU  - Tamakoshi,A
AU  - Thysell,E
AU  - Tsai,CJ
AU  - Tsugane,S
AU  - Vatten,L
AU  - Weiderpass,E
AU  - Weinstein,SJ
AU  - Wilkens,LR
AU  - Yeap,BB
AU  - Allen,NE
AU  - Key,TJ
AU  - Travis,RC
DO  - 10.1002/ijc.34116
EP  - 1046
PY  - 2022///
SN  - 0020-7136
SP  - 1033
TI  - Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia
T2  - International Journal of Cancer
UR  - http://dx.doi.org/10.1002/ijc.34116
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000807068200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ijc.34116
UR  - http://hdl.handle.net/10044/1/102935
VL  - 151
ER  -

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