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@ARTICLE{Niedermaier:178590,
      author       = {T. Niedermaier$^*$ and Y. Balavarca$^*$ and A. Gies$^*$ and
                      K. Weigl$^*$ and F. Guo$^*$ and E. Alwers$^*$ and M.
                      Hoffmeister$^*$ and H. Brenner$^*$},
      title        = {{V}ariation of positive predictive values of fecal
                      immunochemical tests by polygenic risk score in a large
                      screening cohort.},
      journal      = {Clinical and translational gastroenterology},
      volume       = {13},
      number       = {3},
      issn         = {2155-384X},
      address      = {London},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2022-00139},
      pages        = {e00458},
      year         = {2022},
      note         = {#EA:C070#LA:C070#LA:C120# / 2022 Jan 19;13(3):e00458},
      abstract     = {Prevalence of colorectal neoplasms varies by polygenic risk
                      scores (PRS). We aimed to assess to what extent PRS might be
                      relevant for defining personalized cutoff values for fecal
                      immunochemical tests (FITs) in colorectal cancer (CRC)
                      screening.Among 5,306 participants of screening colonoscopy
                      who provided a stool sample for a quantitative FIT
                      (Ridascreen Hemoglobin or FOB Gold) prior to colonoscopy a
                      PRS was determined, based on the number of risk alleles in
                      140 , single nucleotide polymorphism. Subjects were
                      classified into low, medium and high genetic risk for
                      colorectal neoplasms according to PRS tertiles. We
                      calculated positive predictive values (PPVs) and numbers
                      needed to scope (NNS) to detect one advanced neoplasm (AN)
                      by risk group, and cutoff variation needed to achieve
                      comparable PPVs across risk groups in the samples tested
                      with Ridascreen (N=1,271) and FOB Gold (N=4,035)
                      independently, using cutoffs yielding $85\%,$ $90\%$ or
                      $95\%$ specificity.Performance of both FITs was very similar
                      within each PRS group. For a given cutoff, PPVs were
                      consistently higher by $11\%-15\%$ units in the high-risk
                      PRS group compared to the low-risk group (all P-values
                      <0.05). Correspondingly, numbers needed to scope (NNS) to
                      detect one advanced neoplasm varied from 2 (high PRS, high
                      cutoff) to 5 (low PRS, low cutoff). Conversely, very
                      different FIT cutoffs would be needed to ensure comparable
                      PPVs across PRS groups.PPVs and NNS of FITs varied widely
                      across people with high and low genetic risk score. Further
                      research should evaluate the relevance of these differences
                      for personalized CRC screening.This study was partly funded
                      by grants from the German Research Council (DFG, grant No.
                      BR1704/16-1), the Federal Ministry of Education and Research
                      (BMBF, grant no. 01GL1712), and the German Cancer Aid (No.
                      70113330).},
      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:35060941},
      doi          = {10.14309/ctg.0000000000000458},
      url          = {https://inrepo02.dkfz.de/record/178590},
}