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@ARTICLE{Karunamuni:168960,
      author       = {R. A. Karunamuni and M.-P. Huynh-Le and C. C. Fan and W.
                      Thompson and R. A. Eeles and Z. Kote-Jarai and K. Muir and
                      A. Lophatananon and J. Schleutker and N. Pashayan and J.
                      Batra and H. Grönberg and E. I. Walsh and E. L. Turner and
                      A. Lane and R. M. Martin and D. E. Neal and J. L. Donovan
                      and F. C. Hamdy and B. G. Nordestgaard and C. M. Tangen and
                      R. J. MacInnis and A. Wolk and D. Albanes and C. A. Haiman
                      and R. C. Travis and J. L. Stanford and L. A. Mucci and C.
                      M. L. West and S. F. Nielsen and A. S. Kibel and F. Wiklund
                      and O. Cussenot and S. I. Berndt and S. Koutros and K. D.
                      Sørensen and C. Cybulski and E. M. Grindedal and J. Y. Park
                      and S. A. Ingles and C. Maier and R. J. Hamilton and B. S.
                      Rosenstein and A. Vega and I. S. S. Committee and M.
                      Kogevinas and K. L. Penney and M. R. Teixeira and H.
                      Brenner$^*$ and E. M. John and R. Kaneva and C. J.
                      Logothetis and S. L. Neuhausen and A. Razack and L. F.
                      Newcomb and M. Gamulin and N. Usmani and F. Claessens and M.
                      Gago-Dominguez and P. A. Townsend and M. J. Roobol and W.
                      Zheng and I. G. Mills and O. A. Andreassen and A. M. Dale
                      and T. M. Seibert},
      collaboration = {UKGPCS collaborators and A. BioResource and Collaborators
                      and C. P. Investigators and P. S. S. Committee and P.
                      Consortium},
      title        = {{A}dditional {SNP}s improve risk stratification of a
                      polygenic hazard score for prostate cancer.},
      journal      = {Prostate cancer and prostatic diseases},
      volume       = {24},
      number       = {2},
      issn         = {1476-5608},
      address      = {Basingstoke},
      publisher    = {Stockton Press},
      reportid     = {DKFZ-2021-01162},
      pages        = {532 - 541},
      year         = {2021},
      abstract     = {Polygenic hazard scores (PHS) can identify individuals with
                      increased risk of prostate cancer. We estimated the benefit
                      of additional SNPs on performance of a previously validated
                      PHS (PHS46).180 SNPs, shown to be previously associated with
                      prostate cancer, were used to develop a PHS model in men
                      with European ancestry. A machine-learning approach,
                      LASSO-regularized Cox regression, was used to select SNPs
                      and to estimate their coefficients in the training set
                      (75,596 men). Performance of the resulting model was
                      evaluated in the testing/validation set (6,411 men) with two
                      metrics: (1) hazard ratios (HRs) and (2) positive predictive
                      value (PPV) of prostate-specific antigen (PSA) testing. HRs
                      were estimated between individuals with PHS in the top $5\%$
                      to those in the middle $40\%$ (HR95/50), top $20\%$ to
                      bottom $20\%$ (HR80/20), and bottom $20\%$ to middle $40\%$
                      (HR20/50). PPV was calculated for the top $20\%$ (PPV80) and
                      top $5\%$ (PPV95) of PHS as the fraction of individuals with
                      elevated PSA that were diagnosed with clinically significant
                      prostate cancer on biopsy.166 SNPs had non-zero coefficients
                      in the Cox model (PHS166). All HR metrics showed significant
                      improvements for PHS166 compared to PHS46: HR95/50 increased
                      from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and
                      HR20/50 decreased from 0.41 to 0.34. By contrast, no
                      significant differences were observed in PPV of PSA testing
                      for clinically significant prostate cancer.Incorporating 120
                      additional SNPs (PHS166 vs PHS46) significantly improved HRs
                      for prostate cancer, while PPV of PSA testing remained the
                      same.},
      cin          = {C070 / C120 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33420416},
      doi          = {10.1038/s41391-020-00311-2},
      url          = {https://inrepo02.dkfz.de/record/168960},
}