A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1

Laura Fachal, Antonio Gómez-Caamaño, Gillian C. Barnett, Paula Peleteiro, Ana M. Carballo, Patricia Calvo-Crespo, Sarah L. Kerns, Manuel Sánchez-García, Ramón Lobato-Busto, Leila Dorling, Rebecca M. Elliott, David P. Dearnaley, Matthew R. Sydes, Emma Hall, Neil G. Burnet, Ángel Carracedo, Barry S. Rosenstein, Catharine M.L. West, Alison M. Dunning, Ana Vega

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

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 UK4 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 × 1 -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 × 10-9. 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.

Original languageEnglish
Pages (from-to)891-894
Number of pages4
JournalNature Genetics
Volume46
Issue number8
DOIs
StatePublished - Aug 2014

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