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

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    Authors
    Fachal, L
    Gómez-Caamaño, A
    Barnett, G
    Peleteiro, P
    Carballo, A
    Calvo-Crespo, P
    Kerns, S
    Sánchez-García, M
    Lobato-Busto, R
    Dorling, L
    Elliott, Rebecca M
    Dearnaley, D
    Sydes, M
    Hall, E
    Burnet, N
    Carracedo, A
    Rosenstein, B
    West, Catharine M L
    Dunning, A
    Vega, A
    Show allShow less
    Affiliation
    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.
    Issue Date
    2014-06-29
    
    Metadata
    Show full item record
    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.
    Citation
    A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. 2014: Nat Genet
    Journal
    Nature Genetics
    URI
    http://hdl.handle.net/10541/322891
    DOI
    10.1038/ng.3020
    PubMed ID
    24974847
    Type
    Article
    Language
    en
    ISSN
    1546-1718
    ae974a485f413a2113503eed53cd6c53
    10.1038/ng.3020
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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