Karina Dalsgaard Sørensen

The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition

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DOI

  • K Smith Byrne, Cancer Epidemiology Unit
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  • P N Appleby, Cancer Epidemiology Unit
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  • T J Key, Cancer Epidemiology Unit
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  • M V Holmes
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  • G K Fensom, Cancer Epidemiology Unit. Electronic address: georgina.fensom@ndph.ox.ac.uk.
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  • A Agudo, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
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  • E Ardanaz, Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
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  • H Boeing, Department of Epidemiology, German Institute of Human Nutrition (DIfE) 14558 Potsdam-Rehbrücke, Nuthetal, Germany.
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  • H B Bueno-de-Mesquita
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  • M D Chirlaque, Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Health and Social Sciences, Murcia University, Murcia, Spain.
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  • R Kaaks, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de.
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  • N Larrañaga, CIBER of Epidemiology and Public Health (CIBERESP), Madrid; Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Vitoria-Gasteiz, Spain.
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  • D Palli, Cancer Risk Factors and Life-Style Epidemiology Unit. Institute for Cancer Research, Prevention and Clinical Network - ISPRO, 50141, Florence, Italy.
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  • A Perez-Cornago, Cancer Epidemiology Unit
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  • J R Quirós, Public Health Directorate, Asturias, Spain.
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  • F Ricceri, Unit of Epidemiology, Regional Health Service Azienda Sanitaria Locale Torino 3 (ASL TO3), Grugliasco; Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy.
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  • M J Sánchez, CIBER of Epidemiology and Public Health (CIBERESP), Madrid; Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
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  • G Tagliabue, Department of Preventative and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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  • K K Tsilidis, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
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  • R Tumino, Cancer Registry and Histopathology Unit "Civic - M.P. Arezzo "Hospital ASP Ragusa, Italy.
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  • R T Fortner, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de.
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  • P Ferrari, Nutritional Methodology and Biostatistics Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France.
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  • E Riboli, Department of Epidemiology and Biostatistics, Imperial College London, London, England.
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  • H Lilja
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  • R C Travis, Cancer Epidemiology Unit
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  • The PRACTICAL Consortium

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods.

PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method.

RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP.

CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.

Original languageEnglish
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume30
Issue6
Pages (from-to)983-989
Number of pages7
ISSN0923-7534
DOIs
Publication statusPublished - 1 Jun 2019

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