000143668 001__ 143668 000143668 005__ 20240229112602.0 000143668 0247_ $$2doi$$a10.1093/annonc/mdz121 000143668 0247_ $$2pmid$$apmid:31089709 000143668 0247_ $$2ISSN$$a0923-7534 000143668 0247_ $$2ISSN$$a1569-8041 000143668 0247_ $$2altmetric$$aaltmetric:58826730 000143668 037__ $$aDKFZ-2019-01242 000143668 041__ $$aeng 000143668 082__ $$a610 000143668 1001_ $$aSmith Byrne, K.$$b0 000143668 245__ $$aThe 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. 000143668 260__ $$aOxford$$bOxford Univ. Press$$c2019 000143668 3367_ $$2DRIVER$$aarticle 000143668 3367_ $$2DataCite$$aOutput Types/Journal article 000143668 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1566563939_30392 000143668 3367_ $$2BibTeX$$aARTICLE 000143668 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000143668 3367_ $$00$$2EndNote$$aJournal Article 000143668 520__ $$aMicroseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods.A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method.Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP.In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer. 000143668 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0 000143668 588__ $$aDataset connected to CrossRef, PubMed, 000143668 7001_ $$aAppleby, P. N.$$b1 000143668 7001_ $$aKey, T. J.$$b2 000143668 7001_ $$aHolmes, M. V.$$b3 000143668 7001_ $$aFensom, G. K.$$b4 000143668 7001_ $$aAgudo, A.$$b5 000143668 7001_ $$aArdanaz, E.$$b6 000143668 7001_ $$aBoeing, H.$$b7 000143668 7001_ $$aBueno-de-Mesquita, H. B.$$b8 000143668 7001_ $$aChirlaque, M. D.$$b9 000143668 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, R.$$b10$$udkfz 000143668 7001_ $$aLarrañaga, N.$$b11 000143668 7001_ $$aPalli, D.$$b12 000143668 7001_ $$aPerez-Cornago, A.$$b13 000143668 7001_ $$aQuirós, J. R.$$b14 000143668 7001_ $$aRicceri, F.$$b15 000143668 7001_ $$aSánchez, M. J.$$b16 000143668 7001_ $$aTagliabue, G.$$b17 000143668 7001_ $$aTsilidis, K. K.$$b18 000143668 7001_ $$aTumino, R.$$b19 000143668 7001_ $$aFortner, R. T.$$b20 000143668 7001_ $$aFerrari, P.$$b21 000143668 7001_ $$aConsortium, PRACTICAL$$b22$$eCollaboration Author 000143668 7001_ $$aRiboli, E.$$b23 000143668 7001_ $$aLilja, H.$$b24 000143668 7001_ $$aTravis, R. 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