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@ARTICLE{Watts:179958,
author = {E. L. Watts and A. Perez-Cornago and G. K. Fensom and K.
Smith-Byrne and U. Noor and C. D. Andrews and M. J. Gunter
and M. V. Holmes and R. M. Martin and K. K. Tsilidis and D.
Albanes and A. Barricarte and H. B. Bueno-de-Mesquita and C.
Chen and B. A. Cohn and N. L. Dimou and L. Ferrucci and L.
Flicker and N. D. Freedman and G. G. Giles and E. L.
Giovannucci and G. E. Goodman and C. A. Haiman and G. J.
Hankey and J. Huang and W.-Y. Huang and L. M. Hurwitz and R.
Kaaks$^*$ and P. Knekt and T. Kubo and H. Langseth and G.
Laughlin and L. Le Marchand and T. Luostarinen and R. J.
MacInnis and H. O. Mäenpää and S. Männistö and E. J.
Metter and K. Mikami and L. A. Mucci and A. W. Olsen and K.
Ozasa and D. Palli and K. L. Penney and E. A. Platz and H.
Rissanen and N. Sawada and J. M. Schenk and P. Stattin and
A. Tamakoshi and E. Thysell and C. J. Tsai and S. Tsugane
and L. Vatten and E. Weiderpass and S. J. Weinstein and L.
R. Wilkens and B. B. Yeap and N. E. Allen and T. J. Key and
R. C. Travis and R. A. Eeles and C. A. Haiman and Z.
Kote-Jarai and F. R. Schumacher and S. Benlloch and A. A. A.
Olama and K. R. Muir and S. I. Berndt and D. V. Conti and F.
Wiklund and S. Chanock and Y. Wang and C. M. Tangen and J.
Batra and J. A. Clements and A. BioResource and H. Grönberg
and N. Pashayan and J. Schleutker and D. Albanes and S.
Weinstein and A. Wolk and C. M. L. West and L. A. Mucci and
G. Cancel-Tassin and S. Koutros and K. D. Sørensen and E.
M. Grindedal and D. E. Neal and F. C. Hamdy and J. L.
Donovan and R. C. Travis and R. J. Hamilton and S. A. Ingles
and B. S. Rosenstein and Y.-J. Lu and G. G. Giles and R. J.
MacInnis and A. S. Kibel and A. Vega and M. Kogevinas and K.
L. Penney and J. Y. Park and J. L. Stanford and C. Cybulski
and B. G. Nordestgaard and S. F. Nielsen and H. Brenner$^*$
and C. Maier and J. Kim and E. M. John and M. R. Teixeira
and S. L. Neuhausen and K. De Ruyck and A. Razack and L. F.
Newcomb and D. Lessel and R. Kaneva and N. Usmani and F.
Claessens and P. A. Townsend and J. E. Castelao and M. J.
Roobol and F. Menegaux and K.-T. Khaw and L. Cannon-Albright
and H. Pandha and S. N. Thibodeau and D. J. Hunter and P.
Kraft and W. J. Blot and E. Riboli},
collaboration = {C. PRACTICAL consortium},
title = {{C}irculating free testosterone and risk of aggressive
prostate cancer: prospective and {M}endelian randomization
analyses in international consortia.},
journal = {International journal of cancer},
volume = {151},
number = {7},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2022-01007},
pages = {1033-1046},
year = {2022},
note = {2022 Oct 1;151(7):1033-1046},
abstract = {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 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.},
cin = {C020 / C070},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C070-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35579976},
doi = {10.1002/ijc.34116},
url = {https://inrepo02.dkfz.de/record/179958},
}