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@ARTICLE{Srinivasan:294428,
      author       = {S. Srinivasan and T. Kryza and N. Bock and B. W. C. Tse and
                      K. A. Sokolowski and P. Janaththani and A. Fernando and L.
                      Moya and C. Stephens and Y. Dong and J. Röhl and S.
                      Alinezhad and I. Vela and J. L. Perry-Keene and K. Buzacott
                      and R. Nica and M. Gago-Dominguez and J. Schleutker and C.
                      Maier and K. Muir and C. M. Tangen and H. Gronberg and N.
                      Pashayan and D. Albanes and A. Wolk and J. L. Stanford and
                      S. I. Berndt and L. A. Mucci and S. Koutros and O. Cussenot
                      and K. D. Sorensen and E. M. Grindedal and R. C. Travis and
                      C. A. Haiman and R. J. MacInnis and A. Vega and F. Wiklund
                      and D. E. Neal and M. Kogevinas and K. L. Penney and B. G.
                      Nordestgaard and H. Brenner$^*$ and E. M. John and M.
                      Gamulin and F. Claessens and O. Melander and A. Dahlin and
                      P. Stattin and G. Hallmans and C. Häggström and R.
                      Johansson and E. Thysell and A.-C. Rönn and W. Li and N.
                      Brown and G. Dimeski and B. Shepherd and T. Dadaev and M. N.
                      Brook and A. B. Spurdle and U.-H. Stenman and H. Koistinen
                      and Z. Kote-Jarai and R. J. Klein and H. Lilja and R. C.
                      Ecker and R. Eeles and J. Clements and J. Batra},
      collaboration = {I. Study and P. S. S. Committee and P. Consortium and A. P.
                      C. BioResource},
      othercontributors = {E. Bancroft and E. Page and A. Ardern-Jones and C. Bangma
                          and E. Castro and D. Dearnaley and D. Eccles and G. Evans
                          and J. Eyfjord and A. Falconer and C. Foster and F. C. Hamdy
                          and Ó. Þ. Jóhannsson and V. Khoo and G. Lindeman and J.
                          Lubinski and L. Maehle and A. Millner and C. Mikropoulos and
                          A. Mitra and C. Moynihan and J. Offman and G. Rennert and L.
                          Side and M. Suri and P. Wilson and P. Kumar and A. Antoniou
                          and J. McHugh and H. N. Raghallaigh and R. Hall and N.
                          Taylor and S. Thomas and K. Myhill and M. Hogben and E.
                          McGrowder and D. Keating and D. James and J. Merson and S.
                          Hussain and A. Wood and N. Dennis and P. Ardern-Jones and N.
                          van As and S. Hazell and S. Lewis and P. Pharoah and J.
                          Schalken and A. Sohaib and N. de Souza and P. Cathcart and
                          F. Chingewundoh and M. Perry and J. Bamber and A. Dias and
                          C. Mikropolis and S. Saya and A. Chamberlain and A. B. Da
                          Silva and L. D'Mello and S. Moss and J. Melia and N.
                          Kinsella and J. Sobczak and N. Mcaddy and D. Nicol and C.
                          Ogden and D. Cahill and A. Thompson and C. Woodhouse and V.
                          J. Gnanapragasam and C. Cooper and J. Clark and F. R.
                          Schumacher and S. Benlloch and A. A. A. Olama and S. Chanock
                          and Y. Wang and S. J. Weinstein and C. M. L. West and G.
                          Cancel-Tassin and J. L. Donovan and R. J. Hamilton and S. A.
                          Ingles and B. S. Rosenstein and Y.-J. Lu and G. G. Giles and
                          A. S. Kibel and J. Y. Park and C. Cybulski and S. F. Nielsen
                          and J. Kim and M. R. Teixeira and S. L. Neuhausen and K. De
                          Ruyck and A. Razack and L. F. Newcomb and D. Lessel and R.
                          Kaneva and N. Usmani and P. A. Townsend and J. E. Castelao
                          and R. H. N. van Shaik and F. Menegaux and K.-T. Khaw and L.
                          Cannon-Albright and H. Pandha and S. N. Thibodeau and P.
                          Kraft and W. J. Blot and A. Lophatananon and P. J. Goodman
                          and I. M. Thompson and T. Nordström and A. M. Dunning and
                          T. L. J. Tammela and A. Auvinen and N. Håkansson and G. L.
                          Andriole and R. N. Hoover and M. J. Machiela and E.
                          Giovannucci and L. E. B. Freeman and M. Borre and T. J. Key
                          and L. Le Marchand and X. Sheng and M. C. Southey and R. L.
                          Milne and A. Gómez-Caamaño and L. Fachal and M. Eklund and
                          T. Dierssen-Sotos and G. Castaño-Vinyals and A. Alcaraz and
                          S. Lindström and M. Stampfer and S. E. Bojesen and H. V.
                          Stroomberg and A. Røder and X. Gao and B. Holleczek and B.
                          Schöttker$^*$ and J. Hoegel and T. Schnoeller and T. Kulis
                          and S. Joniau and M. E. Martinez and M. Aly and W. Tilley
                          and G. P. Risbridger and L. Horvath and R. Taylor and L.
                          Butler and A.-M. Haynes and M. Papargiris and I. Vela},
      title        = {{A} {PSA} {SNP} associates with cellular function and
                      clinical outcome in men with prostate cancer.},
      journal      = {Nature Communications},
      volume       = {15},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2024-02257},
      pages        = {9587},
      year         = {2024},
      abstract     = {Genetic variation at the 19q13.3 KLK locus is linked with
                      prostate cancer susceptibility in men. The non-synonymous
                      KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536
                      T > C; Ile163Thr-substitution in PSA) is associated with
                      reduced prostate cancer risk, however, the functional
                      relevance is unknown. Here, we identify that the SNP
                      variant-induced change in PSA biochemical activity mediates
                      prostate cancer pathogenesis. The 'Thr' PSA variant leads to
                      small subcutaneous tumours, supporting reduced prostate
                      cancer risk. However, 'Thr' PSA also displays higher
                      metastatic potential with pronounced osteolytic activity in
                      an experimental metastasis in-vivo model. Biochemical
                      characterisation of this PSA variant demonstrates markedly
                      reduced proteolytic activity that correlates with
                      differences in in-vivo tumour burden. The SNP is associated
                      with increased risk for aggressive disease and prostate
                      cancer-specific mortality in three independent cohorts,
                      highlighting its critical function in mediating metastasis.
                      Carriers of this SNP allele have reduced serum total PSA and
                      a higher free/total PSA ratio that could contribute to late
                      biopsy decisions and delay in diagnosis. Our results provide
                      a molecular explanation for the prominent 19q13.3 KLK locus,
                      rs17632542 SNP, association with a spectrum of prostate
                      cancer clinical outcomes.},
      keywords     = {Male / Humans / Prostatic Neoplasms: genetics / Prostatic
                      Neoplasms: pathology / Prostatic Neoplasms: metabolism /
                      Prostatic Neoplasms: mortality / Polymorphism, Single
                      Nucleotide / Prostate-Specific Antigen: blood /
                      Prostate-Specific Antigen: metabolism / Kallikreins:
                      genetics / Kallikreins: metabolism / Genetic Predisposition
                      to Disease / Aged / Animals / Chromosomes, Human, Pair 19:
                      genetics / Middle Aged / Mice / Alleles / Cell Line, Tumor /
                      Prostate-Specific Antigen (NLM Chemicals) / Kallikreins (NLM
                      Chemicals) / KLK3 protein, human (NLM Chemicals)},
      cin          = {C070 / C120 / HD01},
      ddc          = {500},
      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:39505858},
      doi          = {10.1038/s41467-024-52472-6},
      url          = {https://inrepo02.dkfz.de/record/294428},
}