@article{01H8HSXR14CP6Z8FACN7R156MH,
  abstract     = {{Background and purpose: 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. Materials and Methods: 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. Results: 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), breastoedema 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 x 10-8), and arm lymphoedema grade > 1 with rs643644 (p = 3.54 x 10-8). Heritability estimates across significant 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. Conclusions: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints. (c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 187 (2023) 1-10 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).}},
  articleno    = {{109806}},
  author       = {{Jandu, Harkeran K. and Veal, Colin D. and Fachal, Laura and Luccarini, Craig and Aguado-Barrera, Miguel E. and Altabas, Manuel and Azria, David and Baten, Adinda and Bourgier, Celine and Bultijnck, Renée and Colciago, Riccardo R. and Farcy-Jacquet, Marie-Pierre and Chang-Claude, Jenny and Choudhury, Ananya and Dunning, Alison and Elliott, Rebecca M. and Green, Sheryl and Gutiérrez-Enríquez, Sara and Herskind, Carsten and Lambrecht, Maarten and Monten, Christel and Rancati, Tiziana and Reyes, Victoria and Rosenstein, Barry S. and De Ruysscher, Dirk and Carmen De Santis, Maria and Seibold, Petra and Sperk, Elena and Veldwijk, Marlon and Paul Symonds, R. and Stobart, Hilary and Taboada-Valladares, Begoña and Vega, Ana and Veldeman, Liv and Webb, Adam J. and Weltens, Caroline and West, Catharine M. and Rattay, Tim and Talbot, Christopher J. and Consortium, REQUITE}},
  issn         = {{0167-8140}},
  journal      = {{RADIOTHERAPY AND ONCOLOGY}},
  keywords     = {{Radiology, Nuclear Medicine and imaging,Oncology,Hematology,Breast Cancer,Radiotherapy,Radiotherapy side effects,Chronic toxicity,Genome-wide association study,Radiogenomics}},
  language     = {{eng}},
  pages        = {{10}},
  publisher    = {{Elsevier BV}},
  title        = {{Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer}},
  url          = {{http://doi.org/10.1016/j.radonc.2023.109806}},
  volume       = {{187}},
  year         = {{2023}},
}

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