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Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.
Watts, Eleanor L; Perez-Cornago, Aurora; Fensom, Georgina K; Smith-Byrne, Karl; Noor, Urwah; Andrews, Colm D; Gunter, Marc J; Holmes, Michael V; Martin, Richard M; Tsilidis, Konstantinos K; Albanes, Demetrius; Barricarte, Aurelio; Bueno-de-Mesquita, Bas; Chen, Chu; Cohn, Barbara A; Dimou, Niki L; Ferrucci, Luigi; Flicker, Leon; Freedman, Neal D; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Haiman, Christopher A; Hankey, Graeme J; Huang, Jiaqi; Huang, Wen-Yi; Hurwitz, Lauren M; Kaaks, Rudolf; Knekt, Paul; Kubo, Tatsuhiko; Langseth, Hilde; Laughlin, Gail; Le Marchand, Loic; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Mikami, Kazuya; Mucci, Lorelei A; Olsen, Anja W; Ozasa, Kotaro; Palli, Domenico; Penney, Kathryn L; Platz, Elizabeth A; Rissanen, Harri; Sawada, Norie; Schenk, Jeannette M; Stattin, Pär; Tamakoshi, Akiko.
Afiliação
  • Watts EL; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Perez-Cornago A; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Fensom GK; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Smith-Byrne K; Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
  • Noor U; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Andrews CD; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Gunter MJ; Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Holmes MV; Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Martin RM; Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, UK.
  • Tsilidis KK; Department of Population Health Sciences, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Albanes D; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Barricarte A; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK.
  • Bueno-de-Mesquita B; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Chen C; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Cohn BA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Dimou NL; Navarra Public Health Institute, Pamplona, Spain.
  • Ferrucci L; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
  • Flicker L; CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
  • Freedman ND; Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), The Netherlands.
  • Giles GG; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Giovannucci EL; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
  • Goodman GE; Department of Otolaryngology: Head and Neck Surgery, School of Medicine, University of Washington, Seattle, Washington, USA.
  • Haiman CA; Child Health and Development Studies, Public Health Institute, Berkeley, California, USA.
  • Hankey GJ; Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Huang J; National Institute on Aging, Baltimore, Maryland, USA.
  • Huang WY; Medical School, University of Western Australia, Perth, Western Australia, Australia.
  • Hurwitz LM; Western Australian Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia.
  • Kaaks R; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Knekt P; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Kubo T; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Langseth H; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia.
  • Laughlin G; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Le Marchand L; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Luostarinen T; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • MacInnis RJ; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Mäenpää HO; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.
  • Männistö S; Medical School, University of Western Australia, Perth, Western Australia, Australia.
  • Metter EJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Mikami K; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
  • Mucci LA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Olsen AW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Ozasa K; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Palli D; Department of Public Health and Welfare, National Institute for Health and Welfare, Helsinki, Finland.
  • Penney KL; Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Platz EA; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Rissanen H; Department of Research, Cancer Registry of Norway, Oslo, Norway.
  • Sawada N; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California, USA.
  • Schenk JM; University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
  • Stattin P; Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
  • Tamakoshi A; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Int J Cancer ; 151(7): 1033-1046, 2022 10 01.
Article em En | MEDLINE | ID: mdl-35579976
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 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.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Prostata Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Globulina de Ligação a Hormônio Sexual Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Int J Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Prostata Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Globulina de Ligação a Hormônio Sexual Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Int J Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Reino Unido