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@ARTICLE{Mcwilliam:296138,
      author       = {A. Mcwilliam and D. Marshall and S. L. Kerns and G. C.
                      Barnett and A. Vega and T. Kapouranis and M. E. Aguado
                      Barrera and B. Avuzzi and D. Azria and J. Chang-Claude$^*$
                      and A. Choudhury and C. Coedo Costa and A. Dunning and M.-P.
                      Farcy-Jacquet and C. Faivre-Finn and S. Gutiérrez-Enríquez
                      and O. Fuentes Río and A. Gómez Caamaño and M. Lambrecht
                      and C. López Pleguezuelos and T. Rancati and T. Rattay and
                      D. De Ruysscher and P. Seibold$^*$ and E. Sperk and C.
                      Talbot and A. Webb and L. Veldeman and B. S. Rosenstein and
                      C. M. L. West},
      collaboration = {R. Consortium},
      title        = {{A}ssociation of radiation-induced normal tissue toxicity
                      with a high genetic risk for rheumatoid arthritis.},
      journal      = {Journal of the National Cancer Institute},
      volume       = {117},
      number       = {5},
      issn         = {0027-8874},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2025-00068},
      pages        = {1018–1026},
      year         = {2025},
      note         = {Volume 117, Issue 5, May 2025, Pages 1018–1026},
      abstract     = {Overlapping genes are involved with rheumatoid arthritis
                      (RA) and DNA repair pathways. Therefore, we hypothesised
                      that patients with a high polygenic risk score (PRS) for RA
                      will have an increased risk of radiotherapy (RT) toxicity
                      given the involvement of DNA repair.Primary analysis was
                      performed on 1494 prostate cancer, 483 lung cancer and 1820
                      breast cancer patients assessed for development of RT
                      toxicity in the REQUITE study. Validation cohorts were
                      available from the Radiogenomics Consortium. All patients
                      had undergone curative-intent radiotherapy and were assessed
                      prospectively for toxicity. Germline genomic data was
                      available for all patients, allowing a PRS to be calculated
                      using 101 RA risk variants. PRS was analysed as a continuous
                      variable and with >90th percentile cut-off. Associations
                      with acute and late standardised total average toxicity
                      (STAT) scores and individual toxicity end-points were
                      analysed in multivariable models with preselected adjustment
                      variables.Increasing PRS for RA did not increase the risk of
                      acute or late STAT in any cohort. There was an increased
                      risk of late oesophagitis in the lung cancer cohort
                      (coefficient 0.018, p = .01), however this was not validated
                      (p = .79). No individual acute or late toxicity endpoints
                      were significantly associated with PRS for the prostate or
                      breast cohorts. No significant results were found in the
                      validation cohorts in multivariable models.Patients with a
                      high genetic risk for RA do not show increased levels of
                      toxicity after radiotherapy suggesting treatment planning
                      does not need to be modified for such patients.},
      keywords     = {Polygenetic risk scores (Other) / Radiotherapy toxicity
                      (Other) / Rheumatoid arthritis (Other)},
      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:39761002},
      doi          = {10.1093/jnci/djae349},
      url          = {https://inrepo02.dkfz.de/record/296138},
}