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@ARTICLE{Archambault:148822,
      author       = {A. N. Archambault and Y.-R. Su and J. Jeon and M. Thomas
                      and Y. Lin and D. V. Conti and A. K. Win and L. C. Sakoda
                      and I. Lansdorp-Vogelaar and E. F. Peterse and A. G. Zauber
                      and D. Duggan and A. N. Holowatyj and J. R. Huyghe and H.
                      Brenner$^*$ and M. Cotterchio and S. Bézieau and S. L.
                      Schmit and C. K. Edlund and M. C. Southey and R. J. MacInnis
                      and P. T. Campbell and J. Chang-Claude$^*$ and M. L.
                      Slattery and A. T. Chan and A. D. Joshi and M. Song and Y.
                      Cao and M. O. Woods and E. White and S. J. Weinstein and C.
                      M. Ulrich and M. Hoffmeister$^*$ and S. A. Bien and T. A.
                      Harrison and J. Hampe and C. I. Li and C. Schafmayer and K.
                      Offit and P. D. Pharoah and V. Moreno and A. Lindblom and A.
                      Wolk and A. H. Wu and L. Li and M. J. Gunter and A. Gsur and
                      T. O. Keku and R. Pearlman and D. T. Bishop and S.
                      Castellví-Bel and L. Moreira and P. Vodicka and E. Kampman
                      and G. G. Giles and D. Albanes and J. A. Baron and S. I.
                      Berndt and S. Brezina and S. Buch and D. D. Buchanan and A.
                      Trichopoulou and G. Severi and M.-D. Chirlaque and M.-J.
                      Sánchez and D. Palli and T. Kühn$^*$ and N. Murphy and A.
                      J. Cross and A. N. Burnett-Hartman and S. J. Chanock and A.
                      d. l. Chapelle and D. F. Easton and F. Elliott and D. R.
                      English and E. J. Feskens and L. M. FitzGerald and P. J.
                      Goodman and J. L. Hopper and T. J. Hudson and D. J. Hunter
                      and E. J. Jacobs and C. E. Joshu and S. Küry and S. D.
                      Markowitz and R. L. Milne and E. A. Platz and G. Rennert and
                      H. S. Rennert and F. R. Schumacher and R. S. Sandler and D.
                      Seminara and C. M. Tangen and S. N. Thibodeau and A. E.
                      Toland and F. J. van Duijnhoven and K. Visvanathan and L.
                      Vodickova and J. D. Potter and S. Männistö and K.
                      Weigl$^*$ and J. Figueiredo and V. Martín and S. C. Larsson
                      and P. S. Parfrey and W.-Y. Huang and H.-J. Lenz and J. E.
                      Castelao and M. Gago-Dominguez and V. Muñoz-Garzón and C.
                      Mancao and C. A. Haiman and L. R. Wilkens and E. Siegel and
                      E. Barry and B. Younghusband and B. Van Guelpen and S.
                      Harlid and A. Zeleniuch-Jacquotte and P. S. Liang and M. Du
                      and G. Casey and N. M. Lindor and L. Le Marchand and S. J.
                      Gallinger and M. A. Jenkins and P. A. Newcomb and S. B.
                      Gruber and R. E. Schoen and H. Hampel and D. A. Corley and
                      L. Hsu and U. Peters and R. B. Hayes},
      title        = {{C}umulative {B}urden of {C}olorectal {C}ancer-{A}ssociated
                      {G}enetic {V}ariants is {M}ore {S}trongly {A}ssociated
                      {W}ith {E}arly-onset vs {L}ate-onset {C}ancer.},
      journal      = {Gastroenterology},
      volume       = {158},
      number       = {5},
      issn         = {0016-5085},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {Saunders},
      reportid     = {DKFZ-2020-00014},
      pages        = {1274-1286.e12},
      year         = {2020},
      note         = {2020 Apr;158(5):1274-1286.e12.},
      abstract     = {Early-onset colorectal cancer (CRC, in persons younger than
                      50 years old) is increasing in incidence; yet, in the
                      absence of a family history of CRC, this population lacks
                      harmonized recommendations for prevention. We aimed to
                      determine whether a polygenic risk score (PRS) developed
                      from 95 CRC-associated common genetic risk variants was
                      associated with risk for early-onset CRC.We studied risk for
                      CRC associated with a weighted PRS in 12,197 participants
                      younger than 50 years old vs 95,865 participants 50 years or
                      older. PRS was calculated based on single-nucleotide
                      polymorphisms associated with CRC in a large-scale
                      genome-wide association study as of January 2019.
                      Participants were pooled from 3 large consortia that
                      provided clinical and genotyping data: the Colon Cancer
                      Family Registry, the Colorectal Transdisciplinary study, and
                      the Genetics and Epidemiology of Colorectal Cancer
                      Consortium and were all of genetically defined European
                      descent. Findings were replicated in an independent cohort
                      of 72,573 participants.Overall associations with CRC per
                      standard deviation of PRS were significant for early-onset
                      cancer, and were stronger compared with late-onset cancer (P
                      for interaction=.01); when we compared the highest PRS
                      quartile with the lowest, risk increased 3.7-fold for
                      early-onset CRC $(95\%$ CI, 3.28-4.24) vs 2.9-fold for
                      late-onset CRC $(95\%$ CI, 2.80-3.04). This association was
                      strongest for participants without a first-degree family
                      history of CRC (P for interaction=5.61x10-5). When we
                      compared the highest with the lowest quartiles in this
                      group, risk increased 4.3-fold for early-onset CRC $(95\%$
                      CI, 3.61-5.01) vs 2.9-fold for late-onset CRC $(95\%$ CI,
                      2.70-3.00). Sensitivity analyses were consistent with these
                      findings.In an analysis of associations with CRC per
                      standard deviation of PRS, we found the cumulative burden of
                      CRC-associated common genetic variants to associate with
                      early-onset cancer, and to be more strongly associated with
                      early-onset than late-onset cancer-particularly in the
                      absence of CRC family history. Analyses of PRS, along with
                      environmental and lifestyle risk factors, might identify
                      younger individuals who would benefit from preventative
                      measures.},
      cin          = {C070 / C120 / HD01 / C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31866242},
      doi          = {10.1053/j.gastro.2019.12.012},
      url          = {https://inrepo02.dkfz.de/record/148822},
}