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@ARTICLE{Yu:156719,
      author       = {H. Yu$^*$ and J. Raut$^*$ and B. Schöttker$^*$ and B.
                      Holleczek$^*$ and Y. Zhang$^*$ and H. Brenner$^*$},
      title        = {{I}ndividual and joint contributions of genetic and
                      methylation risk scores for enhancing lung cancer risk
                      stratification: data from a population-based cohort in
                      {G}ermany.},
      journal      = {Clinical epigenetics},
      volume       = {12},
      number       = {1},
      issn         = {1868-7083},
      address      = {[S.l.]},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2020-01057},
      pages        = {89},
      year         = {2020},
      note         = {#EA:C070#LA:C070#},
      abstract     = {Risk stratification for lung cancer (LC) screening is so
                      far mostly based on smoking history. This study aimed to
                      assess if and to what extent such risk stratification could
                      be enhanced by additional consideration of genetic risk
                      scores (GRSs) and epigenetic risk scores defined by DNA
                      methylation.We conducted a nested case-control study of 143
                      incident LC cases and 1460 LC-free controls within a
                      prospective cohort of 9949 participants aged 50-75 years
                      with 14-year follow-up. Lifetime smoking history was
                      obtained in detail at recruitment. We built a GRS based on
                      31 previously identified LC-associated single-nucleotide
                      polymorphisms (SNPs) and a DNA methylation score (MRS) based
                      on methylation of 151 previously identified
                      smoking-associated cytosine-phosphate-guanine (CpG) loci. We
                      evaluated associations of GRS and MRS with LC incidence by
                      logistic regression models, controlling for age, sex,
                      smoking status, and pack-years. We compared the predictive
                      performance of models based on pack-years alone with models
                      additionally including GRS and/or MRS using the area under
                      the receiver operating characteristic curve (AUC), net
                      reclassification improvement (NRI), and integrated
                      discrimination improvement (IDI).GRS and MRS showed moderate
                      and strong associations with LC risk even after
                      comprehensive adjustment for smoking history (adjusted odds
                      ratio $[95\%$ CI] comparing highest with lowest quartile
                      1.93 [1.05-3.71] and 5.64 [2.13-17.03], respectively).
                      Similar associations were also observed within the risk
                      groups of ever and heavy smokers. Addition of GRS and MRS
                      furthermore strongly enhanced LC prediction beyond
                      prediction by pack-years (increase of optimism-corrected AUC
                      among heavy smokers from 0.605 to 0.654, NRI $26.7\%,$ p =
                      0.0106, IDI $3.35\%,$ p = 0.0036), the increase being mostly
                      attributable to the inclusion of MRS.Consideration of MRS,
                      by itself or in combination with GRS, may strongly enhance
                      LC risk stratification.},
      cin          = {C070 / C120 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32552915},
      pmc          = {pmc:PMC7301507},
      doi          = {10.1186/s13148-020-00872-y},
      url          = {https://inrepo02.dkfz.de/record/156719},
}