A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. Nat Genet 2014 Aug;46(8):891-4
Date
07/01/2014Pubmed ID
24974847DOI
10.1038/ng.3020Scopus ID
2-s2.0-84905580203 (requires institutional sign-in at Scopus site) 109 CitationsAbstract
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.
Author List
Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, Kerns SL, Sánchez-García M, Lobato-Busto R, Dorling L, Elliott RM, Dearnaley DP, Sydes MR, Hall E, Burnet NG, Carracedo Á, Rosenstein BS, West CM, Dunning AM, Vega AAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chromosomes, Human, Pair 2Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Radiation Injuries
Radiotherapy
Spain
