title: A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1.
abstract: There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity. However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype, which could emerge years after the completion of treatment. We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy (EBRT). The replication cohorts consisted of 633 cases from the UK and 368 cases from North America. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity=6.85×10(-9), odds ratio (OR)=6.61, 95% confidence interval (CI)=2.23-19.63) was replicated in the second stage (lowest unadjusted P value for overall late toxicity=2.08×10(-4), OR=6.17, 95% CI=2.25-16.95; Pcombined=4.16×10(-10)). The inclusion of the third cohort gave unadjusted Pcombined=4.64×10(-11). These results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage.
authors: 1] Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain. [2] Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
authors: Laura
authors: 0000000272569752
authors: L
authors: Fachal
authors: Department of Radiation Oncology, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Antonio
authors: A
authors: Gómez-Caamaño
authors: Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors: Gillian C
authors: GC
authors: Barnett
authors: Department of Radiation Oncology, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Paula
authors: P
authors: Peleteiro
authors: Department of Radiation Oncology, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Ana M
authors: AM
authors: Carballo
authors: Department of Radiation Oncology, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Patricia
authors: P
authors: Calvo-Crespo
authors: Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Sarah L
authors: SL
authors: Kerns
authors: Department of Medical Physics, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Manuel
authors: M
authors: Sánchez-García
authors: Department of Medical Physics, USC University Hospital Complex, SERGAS, Santiago de Compostela, Spain.
authors: Ramón
authors: R
authors: Lobato-Busto
authors: Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors: Leila
authors: L
authors: Dorling
authors: Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital, Manchester, UK.
authors: Rebecca M
authors: RM
authors: Elliott
authors: Institute of Cancer Research and Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, UK.
authors: David P
authors: DP
authors: Dearnaley
authors: Cancer and Other Non-Infectious Diseases, Medical Research Council (MRC) Clinical Trials Unit, London, UK.
authors: Matthew R
authors: 0000000293231371
authors: MR
authors: Sydes
authors: Clinical Trials and Statistics Unit, Institute of Cancer Research, London, UK.
authors: Emma
authors: E
authors: Hall
authors: Department of Oncology, University of Cambridge, Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Neil G
authors: NG
authors: Burnet
authors: 1] Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain. [2] Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain. [3] Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Ángel
authors: Á
authors: Carracedo
authors: Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Barry S
authors: BS
authors: Rosenstein
authors: Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital, Manchester, UK.
authors: Catharine M L
authors: CM
authors: West
authors: Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors: Alison M
authors: AM
authors: Dunning
authors: 1] Fundación Pública Galega de Medicina Xenómica, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain. [2] Grupo de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
authors: Ana
authors: A
authors: Vega
mesh_terms: D002889:Chromosomes, Human, Pair 2 / Q000528:radiation effects*; D056426:Genetic Loci / Q000528:radiation effects*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D013030:Spain