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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/382| Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200,000 men in UK Biobank | |
| Karl Smith Byrne Naomi E Allen Marc J Gunter Richard M Martin Ruth C Travis Bu B Yeap Neil Murphy Konstantinos K Tsilidis Timothy J Key Michael V Holmes Eleanor L Watts Aurora Perez-Cornago Georgina K Fensom Anika Knuppel | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución-SinDerivadas | |
| 10.1101/2020.03.27.20044941 | |
| Background: Insulin-like growth factor-I (IGF-I) and testosterone have been implicated in prostate cancer aetiology. Using newly available data from a large prospective full-cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we aimed to investigate the associations of circulating concentrations of IGF-I, sex hormone-binding globulin (SHBG), total and calculated free testosterone with prostate cancer risk. Patients and methods: For prospective analyses of prostate cancer incidence and mortality, we studied 199,698 male UK Biobank participants using Cox proportional hazards models. Multivariable-adjusted hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample of up to 7,776 men. A 2-sample Mendelian randomization (MR) analysis of IGF-I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from 79,148 cases and 61,106 controls from the PRACTICAL consortium. We used cis- and all (cis and trans) SNP MR approaches. Results: After a mean follow-up of 6.9 years, 5,402 men were diagnosed with and 295 died from prostate cancer. Higher circulating IGF-I was associated with an elevated risk (HR per 5 nmol/L increment=1.09, 95% CI 1.05-1.12) and prostate cancer mortality (HR per 5 nmol/L increment=1.15,1.02-1.29) in observational analyses. Cis- and all SNPs MR analyses also supported the role of IGF-I in prostate cancer diagnosis (cis-MR odds ratio per 5 nmol/L increment=1.34,1.07-1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment=1.10,1.05-1.15), and higher SHBG was associated with a lower risk of prostate cancer (HR per 10 nmol/L increment=0.95,0.94-0.97), but neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. Conclusion(s): These findings implicate IGF-I and free testosterone in prostate cancer development and/or progression. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Cancer Research UK (grant numbers C8221/A19170, C8221/A20986 and C8221/A29017). ELW was supported by the Nuffield Department of Population Health Early Career Research Fellowship. AK is supported by the Wellcome Trust (LEAP 205212/Z/16/Z). MVH works in a unit that receives funding from the UK Medical Research Council and is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Centre. RMM was supported by a Cancer Research UK (C18281/A19169) programme grant (the Integrative Cancer Epidemiology Programme) and is part of the Medical Research Council Integrative Epidemiology Unit at the University of Bristol supported by the Medical Research Council (MC_UU_12013/1, MC_UU_12013/2, and MC_UU_12013/3) and the University of Bristol. RMM is also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre which is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. KKT was funded by the Small Research Teams funding programme from the Hellenic Republic, Ministry of Education. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes UK Biobank data are available through a procedure described at http://www.ukbiobank.ac.uk/using-the-resource/. IGF1 GWAS data are publicly available from: http://www.nealelab.is/uk-biobank. PRACTICAL data may be available on application: http://practical.icr.ac.uk/blog/ <http://www.ukbiobank.ac.uk/using-the-resource/> <http://www.nealelab.is/uk-biobank> <http://practical.icr.ac.uk/blog/> | |
| Cold Spring Harbor Laboratory Press | |
| 2020 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/2020.03.27.20044941v1 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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