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

Research output: Contribution to journalArticle


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.


  • K. Smith Byrne
  • P. N. Appleby
  • T. J. Key
  • M. V. Holmes
  • G. K. Fensom
  • A. Agudo
  • E. Ardanaz
  • H. Boeing
  • H. B. Bueno-De-Mesquita
  • M. D. Chirlaque
  • R. Kaaks
  • N. Larranãga
  • D. Palli
  • A. Perez-Cornago
  • J. R. Quirós
  • F. Ricceri
  • M. J. Sánchez
  • G. Tagliabue
  • K. K. Tsilidis
  • R. Tumino
  • R. T. Fortner
  • P. Ferrari
  • E. Riboli
  • R. C. Travis
External organisations
  • University of Oxford
  • University of Bristol
  • Bellvitge Biomedical Research Institute
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Health Research Institute of Navarra (IDISNA)
  • German Institute of Human Nutrition
  • National Institute for Public Health and the Environment (RIVM)
  • Imperial College London
  • University of Malaya
  • University of Murcia
  • German Cancer Research Centre
  • Institute for Cancer Research, Prevention and Clinical Network (ISPRO)
  • Public Health Directorate
  • University of Turin
  • Andalusian School of Public Health
  • Istituto Nazionale dei Tumori
  • University of Ioannina
  • Civic and M.P Arezzo Hospital
  • International Agency for Research on Cancer, World Health Organization
  • Memorial Sloan-Kettering Cancer Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • EPIC cohort, Mendelian randomization, microseminoprotein-beta, prospective study, prostate cancer, prostate-specific antigen
Original languageEnglish
Article numbermdz121
Pages (from-to)983-989
Number of pages7
JournalAnnals of Oncology
Issue number6
Publication statusPublished - 2019 Jun 1
Publication categoryResearch