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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 |
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We thank all participants, researchers and support staff who made the study possible. CARET would like to acknowledge the support of Frank Z. Stanczyk, S. Kay. Lewis, Ruth Etzioni, Matt Barnett, Dante DiTommaso, and the CARET study participants. CHDS would like to acknowledge the support of Alice Whittemore and David Feldman. CLUE thank Kathy J. Helzlsouer for her contributions to the cohort and thank the staff and participants of the CLUE study for their important contributions. Cancer data were provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund. The collection and availability of cancer registry data is also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services. The authors would like to thank Paul Appleby for past contributions to establishing the EHNBPCCG dataset and related coding. We additionally thank investigators from EPIC Norfolk, JHCS, and MMAS for contributing data. Cancer Research UK, Grant/Award Numbers: C18281/A29019, C60192/A28516, C8221/A19170, C8221/A29017; National Cancer Institute, Grant/Award Numbers: R01‐CA 78812, U01‐CA063673, U01‐CA167462, UM1‐CA167462; National Institutes of Health, Grant/Award Numbers: IU01AG18033, IU01CA86308, U01 CA164973; World Cancer Research Fund, Grant/Award Number: 2019/1953 Funding information Centralised pooling, checking and data analysis were supported by Cancer Research UK (grant numbers C8221/A19170 and C8221/A29017). Eleanor L. Watts is supported by the Nuffield Department of Population Health Early Career Research Fellowship. Aurora Perez‐Cornago is supported by a Cancer Research UK Population Research Fellowship (C60192/A28516) and by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (2019/1953). ATBC was supported in part by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. CARET is funded by the National Cancer Institute, National Institutes of Health through grants U01‐CA063673, UM1‐CA167462, R01‐CA 78812 and U01‐CA167462. CLUE is funded by the American Institute for Cancer Research, NIH Grants IU01AG18033 and IU01CA86308. HIMS was supported by research grants from the National Health and Medical Research Council of Australia. MEC is supported by the US National Institutes of Health grant U01 CA164973. JACC study was supported by Grants‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RMM was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. We thank all participants, researchers and support staff who made the study possible. CARET would like to acknowledge the support of Frank Z. Stanczyk, S. Kay. Lewis, Ruth Etzioni, Matt Barnett, Dante DiTommaso, and the CARET study participants. CHDS would like to acknowledge the support of Alice Whittemore and David Feldman. CLUE thank Kathy J. Helzlsouer for her contributions to the cohort and thank the staff and participants of the CLUE study for their important contributions. Cancer data were provided by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund. The collection and availability of cancer registry data is also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services. The authors would like to thank Paul Appleby for past contributions to establishing the EHNBPCCG dataset and related coding. We additionally thank investigators from EPIC Norfolk, JHCS, and MMAS for contributing data.; https://hdl.handle.net/10138/348083; 85133539795; 000807068200001 |