A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1Citation formats
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A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. / Fachal, Laura; Gómez-Caamaño, Antonio; Barnett, Gillian C.; Peleteiro, Paula; Carballo, Ana M.; Calvo-Crespo, Patricia; Kerns, Sarah L.; Sánchez-García, Manuel; Lobato-Busto, Ramón; Dorling, Leila; Elliott, Rebecca M.; Dearnaley, David P.; Sydes, Matthew R.; Hall, Emma; Burnet, Neil G.; Carracedo, Ángel; Rosenstein, Barry S.; West, Catharine M L; Dunning, Alison M.; Vega, Ana.
In: Nature Genetics, Vol. 46, No. 8, 29.06.2014, p. 891-894.Research output: Contribution to journal › Article › peer-review
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T1 - A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1
AU - Fachal, Laura
AU - Gómez-Caamaño, Antonio
AU - Barnett, Gillian C.
AU - Peleteiro, Paula
AU - Carballo, Ana M.
AU - Calvo-Crespo, Patricia
AU - Kerns, Sarah L.
AU - Sánchez-García, Manuel
AU - Lobato-Busto, Ramón
AU - Dorling, Leila
AU - Elliott, Rebecca M.
AU - Dearnaley, David P.
AU - Sydes, Matthew R.
AU - Hall, Emma
AU - Burnet, Neil G.
AU - Carracedo, Ángel
AU - Rosenstein, Barry S.
AU - West, Catharine M L
AU - Dunning, Alison M.
AU - Vega, Ana
PY - 2014/6/29
Y1 - 2014/6/29
N2 - 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. © 2014 Nature America, Inc.
AB - 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. © 2014 Nature America, Inc.
U2 - 10.1038/ng.3020
DO - 10.1038/ng.3020
M3 - Article
VL - 46
SP - 891
EP - 894
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 8
ER -