% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Barnett:180699,
      author       = {G. C. Barnett and S. L. Kerns and L. Dorling and L. Fachal
                      and M. E. Aguado-Barrera and L. Martínez-Calvo and H. K.
                      Jandu and C. Welsh and J. Tyrer and C. E. Coles and J. S.
                      Haviland and C. Parker and A. Gómez-Caamaño and P.
                      Calvo-Crespo and P. Sosa-Fajardo and N. G. Burnet and H.
                      Summersgill and A. Webb and D. De Ruysscher and P.
                      Seibold$^*$ and J. Chang-Claude$^*$ and C. J. Talbot and T.
                      Rattay and M. Parliament and K. De Ruyck and B. S.
                      Rosenstein and P. D. P. Pharoah and A. M. Dunning and A.
                      Vega and C. M. L. West},
      title        = {{N}o association between polygenic risk scores for cancer
                      and development of radiotherapy toxicity.},
      journal      = {International journal of radiation oncology, biology,
                      physics},
      volume       = {114},
      number       = {3},
      issn         = {0360-3016},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2022-01495},
      pages        = {494-501},
      year         = {2022},
      note         = {2022 Nov 1;114(3):494-501},
      abstract     = {To test whether updated polygenic risk scores (PRS) for
                      susceptibility to cancer affect risk of radiotherapy
                      toxicity.Analyses included 9,717 patients with breast
                      (n=3,078), prostate (n=5,748) or lung (n=891) cancer from
                      XXXX and XXXX Consortia cohorts. Patients underwent
                      potentially curative radiotherapy and were assessed
                      prospectively for toxicity. Germline genotyping involved
                      genome-wide single nucleotide polymorphism (SNP) arrays with
                      non-typed SNPs imputed. PRS for each cancer were generated
                      by summing literature-identified cancer susceptibility risk
                      alleles: 352 breast, 136 prostate, 24 lung. Weighted PRS
                      were generated using log odds ratios for cancer
                      susceptibility. Standardized total average toxicity (STAT)
                      scores at 2 and 5 years (breast, prostate) or 6 to 12 months
                      (lung) quantified toxicity. Primary analysis tested late
                      STAT, secondary analyses investigated acute STAT, and
                      individual endpoints and SNPs using multivariable
                      regression.Increasing PRS did not increase risk of late
                      toxicity in patients with breast (OR 1.000, $95\%CI$
                      0.997-1.002), prostate (OR 0.99, $95\%CI$ 0.98-1.00;
                      weighted PRS OR 0.93, $95\%CI$ 0.83-1.03) or lung (OR 0.93,
                      $95\%CI$ 0.87-1.00; weighted PRS OR 0.68, $95\%CI$
                      0.45-1.03) cancer. Similar results were seen for acute
                      toxicity. Secondary analyses identified rs138944387
                      associated with breast pain (OR=3.05; $95\%CI$ 1.86- 5.01;
                      P=1.09 × 10-5) and rs17513613 with breast oedema (OR=0.94;
                      $95\%CI$ 0.92- 0.97; P=1.08 × 1 0-5).Patients with
                      increased polygenic predisposition to breast, prostate or
                      lung cancer can safely undergo radiotherapy with no
                      anticipated excess toxicity risk. Some individual SNPs
                      increase likelihood of a specific toxicity endpoint
                      warranting validation in independent cohorts and functional
                      studies to elucidate biologic mechanisms.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35840111},
      doi          = {10.1016/j.ijrobp.2022.06.098},
      url          = {https://inrepo02.dkfz.de/record/180699},
}