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@ARTICLE{Jandu:277474,
      author       = {H. K. Jandu and C. D. Veal and L. Fachal and C. Luccarini
                      and M. E. Aguado-Barrera and M. Altabas and D. Azria and A.
                      Baten and C. Bourgier and R. Bultijnck and R. R. Colciago
                      and M.-P. Farcy-Jacquet and J. Chang-Claude$^*$ and A.
                      Choudhury and A. Dunning and R. M. Elliott and S. Green and
                      S. Gutiérrez-Enríquez and C. Herskind and M. Lambrecht and
                      C. Monten and T. Rancati and V. Reyes and B. S. Rosenstein
                      and D. De Ruysscher and M. Carmen De Santis and P.
                      Seibold$^*$ and E. Sperk and M. Veldwijk and R. Paul Symonds
                      and H. Stobart and B. Taboada-Valladares and A. Vega and L.
                      Veldeman and A. J. Webb and C. Weltens and C. M. West and T.
                      Rattay and C. J. Talbot},
      collaboration = {R. consortium},
      title        = {{G}enome-wide association study of treatment-related
                      toxicity two years following radiotherapy for breast
                      cancer.},
      journal      = {Radiotherapy and oncology},
      volume       = {187},
      issn         = {0167-8140},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2023-01395},
      pages        = {109806},
      year         = {2023},
      note         = {Volume 187, October 2023, 109806Radiotherapy and Oncology},
      abstract     = {Up to a quarter of breast cancer patients treated by
                      surgery and radiotherapy experience clinically significant
                      toxicity. If patients at high risk of adverse effects could
                      be identified at diagnosis, their treatment could be
                      tailored accordingly. This study was designed to identify
                      common single nucleotide polymorphisms (SNPs) associated
                      with toxicity two years following whole breast
                      radiotherapy.A genome-wide association study (GWAS) was
                      performed in 1,640 breast cancer patients with complete SNP,
                      clinical, treatment and toxicity data, recruited across 18
                      European and US centres into the prospective REQUITE cohort
                      study. Toxicity data (CTCAE v4.0) were collected at
                      baseline, end of radiotherapy, and annual follow-up. A total
                      of 7,097,340 SNPs were tested for association with the
                      residuals of toxicity endpoints, adjusted for clinical,
                      treatment co-variates and population
                      substructure.Quantile-quantile plots showed more
                      associations with toxicity above the p<5 x 10-5 level than
                      expected by chance. Eight SNPs reached genome-wide
                      significance. Nipple retraction grade≥2 was associated
                      with the rs188287402 variant (p=2.80 x 10-8), breast oedema
                      grade≥2 with rs12657177 (p=1.12 x 10-10), rs75912034 (p=
                      1.12 x 10-10), rs145328458 (p=1.06 x 10-9) and rs61966612
                      (p=1.23 x 10-9), induration grade≥2 with rs77311050
                      (p=2.54 x 10-8) and rs34063419 (p=1.21 × 10-8), and arm
                      lymphoedema grade≥1 with rs643644 (p=3.54 x 10-8).
                      Heritability estimates across different endpoints ranged
                      from $25\%$ to $39\%.$ Our study did not replicate
                      previously reported SNPs associated with breast radiation
                      toxicity at the pre-specified significance level.This GWAS
                      for long-term breast radiation toxicity provides further
                      evidence for significant association of common SNPs with
                      distinct toxicity endpoints.},
      keywords     = {Breast Cancer (Other) / Genome-wide association study
                      (Other) / Late radiotherapy side effects (Other) /
                      Radiogenomics (Other) / Radiotherapy (Other) / late toxicity
                      (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:37437607},
      doi          = {10.1016/j.radonc.2023.109806},
      url          = {https://inrepo02.dkfz.de/record/277474},
}