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@ARTICLE{Giaccherini:282532,
      author       = {M. Giaccherini and L. Gori and M. Gentiluomo and R.
                      Farinella and K. Cervena and J. Skieceviciene and F. Dijk
                      and G. Capurso and A. Vezakis and L. Archibugi and R.
                      Chammas and T. Hussein and F. Tavano and P. Hegyi and M.
                      Lovecek and J. Izbicki and H. Brenner$^*$ and B.
                      Mohelnikova-Duchonova and G. Dell'Anna and J. Kupcinskas and
                      S. Ermini and M. N. Aoki and J. P. Neoptolemos and M.
                      Gazouli and C. Pasquali and R. Pezzilli and R.
                      Talar-Wojnarowska and M. Oliverius and M. Al-Saeedi and M.
                      Lucchesi and N. Furbetta and S. Carrara and C. H. J. van
                      Eijck and A. Maleckas and A. C. Milanetto and R. T. Lawlor
                      and B. Schöttker$^*$ and U. Boggi and L. Morelli and L.
                      Ginocchi and R. Ponz de Leon and C. Sperti and A. Zerbi and
                      P. G. Arcidiacono and F. G. Uzunoglu and S. Bunduc and B.
                      Holleczek and D. Gioffreda and E. Małecka-Wojciesko and M.
                      Kiudelis and A. Szentesi and H. W. M. van Laarhoven and P.
                      Soucek and M. Götz and B. Erőss and G. M. Cavestro and D.
                      Basso and F. Perri and S. Landi and F. Canzian$^*$ and D.
                      Campa},
      title        = {{A} scan of all coding region variants of the human genome,
                      identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel
                      risk loci for pancreatic ductal adenocarcinoma.},
      journal      = {Carcinogenesis},
      volume       = {44},
      number       = {8-9},
      issn         = {0143-3334},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-01812},
      pages        = {642-649},
      year         = {2023},
      note         = {2023 Dec 2;44(8-9):642-649},
      abstract     = {Coding sequence variants comprise a small fraction of the
                      germline genetic variability of the human genome. However,
                      they often cause deleterious change in protein function and
                      are therefore associated with pathogenic phenotypes. To
                      identify novel pancreatic ductal adenocarcinoma (PDAC) risk
                      loci, we carried out a complete scan of all common missense
                      and synonymous SNPs and analysed them in a case control
                      study comprising four different populations, for a total of
                      14,538 PDAC cases and 190,657 controls. We observed a
                      statistically significant association between
                      13q12.2-rs9581957-T and PDAC risk (P=2.46x10 -9), that is in
                      linkage disequilibrium (LD) with a deleterious missense
                      variant (rs9579139) of the URAD gene. Recent findings
                      suggest that this gene is active in peroxisomes. Considering
                      that peroxisomes have a key role as molecular scavengers,
                      especially in eliminating reactive oxygen species, a
                      malfunctioning URAD protein might expose the cell to a
                      higher load of potentially DNA damaging molecules and
                      therefore increase PDAC risk. The association was observed
                      in individuals of European and Asian ethnicity. We also
                      observed the association of the missense variant
                      15q24.1-rs2277598-T, that belongs to BBS4 gene, with
                      increased PDAC risk (P=1.53x10 -6). rs2277598 is associated
                      with body mass index and is in LD with diabetes
                      susceptibility loci. In conclusion, we identified two
                      missense variants associated with the risk of developing
                      PDAC independently from the ethnicity highlighting the
                      importance of conducting reanalysis of GWAS studies in light
                      of functional data.},
      keywords     = {Pancreatic ductal adenocarcinoma (Other) / association
                      study (Other) / genetic susceptibility (Other) / missense
                      (Other) / single nucleotide polymorphisms (Other)},
      cin          = {C070 / C120 / HD01 / C055},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)C055-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37670727},
      doi          = {10.1093/carcin/bgad056},
      url          = {https://inrepo02.dkfz.de/record/282532},
}