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@ARTICLE{Lin:168679,
      author       = {H.-Y. Lin and P.-Y. Huang and C.-H. Cheng and H.-Y. Tung
                      and Z. Fang and A. E. Berglund and A. Chen and J.
                      French-Kwawu and D. Harris and J. Pow-Sang and K. Yamoah and
                      J. L. Cleveland and S. Awasthi and R. J. Rounbehler and T.
                      Gerke and J. Dhillon and R. Eeles and Z. Kote-Jarai and K.
                      Muir and J. Schleutker and N. Pashayan and D. E. Neal and S.
                      F. Nielsen and B. G. Nordestgaard and H. Gronberg and F.
                      Wiklund and G. G. Giles and C. A. Haiman and R. C. Travis
                      and J. L. Stanford and A. S. Kibel and C. Cybulski and K.-T.
                      Khaw and C. Maier and S. N. Thibodeau and M. R. Teixeira and
                      L. Cannon-Albright and H. Brenner$^*$ and R. Kaneva and H.
                      Pandha and S. Srinivasan and J. Clements and J. Batra and J.
                      Y. Park and R. Eeles and Z. Kote-Jarai and K. Muir and J.
                      Clements and J. Batra and H.-Y. Lin and R. Eeles and Z.
                      Kote-Jarai and K. Muir and J. Schleutker and N. Pashayan and
                      D. E. Neal and S. F. Nielsen and B. G. Nordestgaard and H.
                      Gronberg and F. Wiklund and G. G. Giles and C. A. Haiman and
                      R. C. Travis and J. L. Stanford and A. S. Kibel and C.
                      Cybulski and K.-T. Khaw and C. Maier and S. N. Thibodeau and
                      M. R. Teixeira and L. Cannon-Albright and H. Brenner$^*$ and
                      R. Kaneva and H. Pandha},
      collaboration = {UKGPCS collaborators and APCB and P. consortium},
      title        = {{KLK}3 {SNP}-{SNP} interactions for prediction of prostate
                      cancer aggressiveness.},
      journal      = {Scientific reports},
      volume       = {11},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2021-00987},
      pages        = {9264},
      year         = {2021},
      abstract     = {Risk classification for prostate cancer (PCa)
                      aggressiveness and underlying mechanisms remain inadequate.
                      Interactions between single nucleotide polymorphisms (SNPs)
                      may provide a solution to fill these gaps. To identify
                      SNP-SNP interactions in the four pathways (the
                      angiogenesis-, mitochondria-, miRNA-, and androgen
                      metabolism-related pathways) associated with PCa
                      aggressiveness, we tested 8587 SNPs for 20,729 cases from
                      the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P <
                      3.5 × 10-9) and 3145 (P < 1 × 10-5) SNP-SNP interaction
                      pairs significantly associated with PCa aggressiveness.
                      These SNP pairs associated with PCa aggressiveness were more
                      significant than each of their constituent SNP individual
                      effects. The majority $(98.6\%)$ of the 3145 pairs involved
                      KLK3. The 3 most common gene-gene interactions were
                      KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions
                      from the SNP interaction-based polygenic risk score based on
                      24 SNP pairs are promising. The prevalence of PCa
                      aggressiveness was $49.8\%,$ $21.9\%,$ and $7.0\%$ for the
                      PCa cases from our cohort with the top $1\%,$ middle $50\%,$
                      and bottom $1\%$ risk profiles. Potential biological
                      functions of the identified KLK3 SNP-SNP interactions were
                      supported by gene expression and protein-protein interaction
                      results. Our findings suggest KLK3 SNP interactions may play
                      an important role in PCa aggressiveness.},
      cin          = {C070 / C120 / HD01},
      ddc          = {600},
      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:33927218},
      pmc          = {pmc:PMC8084951},
      doi          = {10.1038/s41598-021-85169-7},
      url          = {https://inrepo02.dkfz.de/record/168679},
}