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@ARTICLE{Weigl:136831,
      author       = {K. Weigl$^*$ and H. Thomsen$^*$ and Y. Balavarca$^*$ and J.
                      N. Hellwege and M. J. Shrubsole and H. Brenner$^*$},
      title        = {{G}enetic {R}isk {S}core {I}s {A}ssociated {W}ith
                      {P}revalence of {A}dvanced {N}eoplasms in a {C}olorectal
                      {C}ancer {S}creening {P}opulation.},
      journal      = {Gastroenterology},
      volume       = {155},
      number       = {1},
      issn         = {0016-5085},
      address      = {Stanford, Calif.},
      publisher    = {HighWire Press},
      reportid     = {DKFZ-2018-01269},
      pages        = {88 - 98.e10},
      year         = {2018},
      abstract     = {The presence of specific single nucleotide polymorphisms
                      (SNPs) can be used to calculate an individual's risk for
                      colorectal cancer (CRC), called a genetic risk score (GRS).
                      We investigated whether GRS can identify individuals with
                      clinically relevant neoplasms in a screening colonoscopy
                      population.We derived a GRS based on 48 SNPs associated with
                      CRC, identified in a comprehensive literature search. We
                      obtained genetic data from 1043 participants (50-79 years
                      old) in a screening colonoscopy study in Germany, recruited
                      from 2005 through 2013 (294 with advanced neoplasms, 249
                      with non-advanced adenoma (NAAs), and 500 without
                      neoplasms). Each participant was assigned a GRS by
                      aggregating their risk alleles (0, 1, or 2). Risk of
                      advanced neoplasms and NAA according to GRS was calculated
                      by multiple logistic regression. Risk advancement periods
                      were calculated. We replicated our findings using data from
                      a subset of the Tennessee Colorectal Polyp Study.An
                      increased GRS was associated with higher prevalence of
                      advanced neoplasms, but not NAAs. Participants in the middle
                      and upper tertiles of GRS had a 2.2-fold and 2.7-fold
                      increase in risk, respectively, of advanced neoplasms
                      compared to those in the lower tertile. Adjusted odds ratios
                      (ORs) were 1.09 $(95\%$ confidence interval [CI], 0.76-1.57)
                      for NAA in the middle tertile and 1.05 $(95\%$ CI,
                      0.70-1.55) for NAA in the upper tertile. The ORs were
                      largest for proximal advanced neoplasms for participants in
                      the middle tertile (OR, 3.55; $95\%$ CI 1.85-6.82) and the
                      upper tertile (OR, 3.61; $95\%$ CI 1.84-7.10). The risk
                      advancement period for medium vs low GRS was 13.4 years
                      $(95\%$ CI 4.8-22.0) and for high vs low GRS was 17.5 years
                      $(95\%$ CI, 7.8-27.3).In a genetic analysis of participants
                      in a CRC screening study in Germany, an increased GRS (based
                      on CRC-associated SNPs) was associated with increased
                      prevalence of advanced neoplasms. These findings might be
                      used in defining risk-adapted screening ages.},
      cin          = {C070 / G110 / C050 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
                      I:(DE-He78)C050-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29574091},
      pmc          = {pmc:PMC6035076},
      doi          = {10.1053/j.gastro.2018.03.030},
      url          = {https://inrepo02.dkfz.de/record/136831},
}