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Title: 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
Author: Smith Byrne, K.
Appleby, Paul N.
Key, Timothy J.
Holmes, M. V.
Fensom, G. K.
Agudo, Antonio
Ardanaz, Eva
Boeing, Heiner
Bueno de Mesquita, H. Bas
Chirlaque, María Dolores
Kaaks, Rudolf
Larrañaga, Nerea
Palli, Domenico
Pérez Cornago, Aurora
Quirós, J. Ramón
Ricceri, Fulvio
Sánchez, María José
Tagliabue, Giovanna
Tsilidis, Konstantinos K.
Tumino, Rosario
Fortner, Renée T.
Ferrari, Pietro
Riboli, Elio
Lilja, H.
Travis, Ruth C.
Keywords: Càncer de pròstata
Prostate cancer
Issue Date: 1-Jun-2019
Publisher: Elsevier Inc.
Abstract: 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.
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It is part of: Annals of Oncology, 2019, vol. 30, num. 6, p. 983-989
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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