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

doi:10.1038/ng.3020

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

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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. © 2014 Nature America, Inc.

Original language	English
Pages (from-to)	891-894
Number of pages	3
Journal	Nature Genetics
Volume	46
Issue number	8
DOIs	https://doi.org/10.1038/ng.3020
Publication status	Published - 29 Jun 2014

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Fachal, L., Gómez-Caamaño, A., Barnett, G. C., Peleteiro, P., Carballo, A. M., Calvo-Crespo, P., Kerns, S. L., Sánchez-García, M., Lobato-Busto, R., Dorling, L., Elliott, R. M., Dearnaley, D. P., Sydes, M. R., Hall, E., Burnet, N. G., Carracedo, Á., Rosenstein, B. S., West, C. M. L., Dunning, A. M., & Vega, A. (2014). A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. Nature Genetics, 46(8), 891-894. https://doi.org/10.1038/ng.3020

@article{fd2c5223b3694525acd799e9ac3c4b3d,

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 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. {\textcopyright} 2014 Nature America, Inc.",

author = "Laura Fachal and Antonio G{\'o}mez-Caama{\~n}o and Barnett, {Gillian C.} and Paula Peleteiro and Carballo, {Ana M.} and Patricia Calvo-Crespo and Kerns, {Sarah L.} and Manuel S{\'a}nchez-Garc{\'i}a and Ram{\'o}n Lobato-Busto and Leila Dorling and Elliott, {Rebecca M.} and Dearnaley, {David P.} and Sydes, {Matthew R.} and Emma Hall and Burnet, {Neil G.} and {\'A}ngel Carracedo and Rosenstein, {Barry S.} and West, {Catharine M L} and Dunning, {Alison M.} and Ana Vega",

year = "2014",

month = jun,

day = "29",

doi = "10.1038/ng.3020",

language = "English",

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journal = "Nature Genetics",

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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, CML, Dunning, AM & Vega, A 2014, 'A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1', Nature Genetics, vol. 46, no. 8, pp. 891-894. https://doi.org/10.1038/ng.3020

TY - JOUR

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

SN - 1061-4036

VL - 46

SP - 891

EP - 894

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

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