A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicityCitation formats

  • External authors:
  • Gillian C. Barnett
  • Deborah Thompson
  • Laura Fachal
  • Sarah Kerns
  • Chris Talbot
  • Rebecca M. Elliott
  • Leila Dorling
  • Charlotte E. Coles
  • David P. Dearnaley
  • Barry S. Rosenstein
  • Ana Vega
  • Paul Symonds
  • John Yarnold
  • Caroline Baynes
  • Kyriaki Michailidou
  • Joe Dennis
  • Jonathan P. Tyrer
  • Jennifer S. Wilkinson
  • Antonio Gómez-Caamaño
  • George A. Tanteles
  • Radka Platte
  • Rebecca Mayes
  • Don Conroy
  • Mel Maranian
  • Craig Luccarini
  • Sarah L. Gulliford
  • Matthew R. Sydes
  • Emma Hall
  • Joanne Haviland
  • Vivek Misra
  • Jennifer Titley
  • Søren M. Bentzen
  • Paul D P Pharoah
  • Neil G. Burnet
  • Alison M. Dunning

Standard

A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. / Barnett, Gillian C.; Thompson, Deborah; Fachal, Laura; Kerns, Sarah; Talbot, Chris; Elliott, Rebecca M.; Dorling, Leila; Coles, Charlotte E.; Dearnaley, David P.; Rosenstein, Barry S.; Vega, Ana; Symonds, Paul; Yarnold, John; Baynes, Caroline; Michailidou, Kyriaki; Dennis, Joe; Tyrer, Jonathan P.; Wilkinson, Jennifer S.; Gómez-Caamaño, Antonio; Tanteles, George A.; Platte, Radka; Mayes, Rebecca; Conroy, Don; Maranian, Mel; Luccarini, Craig; Gulliford, Sarah L.; Sydes, Matthew R.; Hall, Emma; Haviland, Joanne; Misra, Vivek; Titley, Jennifer; Bentzen, Søren M.; Pharoah, Paul D P; Burnet, Neil G.; Dunning, Alison M.; West, Catharine M L.

In: Radiotherapy and Oncology, Vol. 111, No. 2, 2014, p. 178-185.

Research output: Contribution to journalArticle

Harvard

Barnett, GC, Thompson, D, Fachal, L, Kerns, S, Talbot, C, Elliott, RM, Dorling, L, Coles, CE, Dearnaley, DP, Rosenstein, BS, Vega, A, Symonds, P, Yarnold, J, Baynes, C, Michailidou, K, Dennis, J, Tyrer, JP, Wilkinson, JS, Gómez-Caamaño, A, Tanteles, GA, Platte, R, Mayes, R, Conroy, D, Maranian, M, Luccarini, C, Gulliford, SL, Sydes, MR, Hall, E, Haviland, J, Misra, V, Titley, J, Bentzen, SM, Pharoah, PDP, Burnet, NG, Dunning, AM & West, CML 2014, 'A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity', Radiotherapy and Oncology, vol. 111, no. 2, pp. 178-185. https://doi.org/10.1016/j.radonc.2014.02.012

APA

Vancouver

Author

Barnett, Gillian C. ; Thompson, Deborah ; Fachal, Laura ; Kerns, Sarah ; Talbot, Chris ; Elliott, Rebecca M. ; Dorling, Leila ; Coles, Charlotte E. ; Dearnaley, David P. ; Rosenstein, Barry S. ; Vega, Ana ; Symonds, Paul ; Yarnold, John ; Baynes, Caroline ; Michailidou, Kyriaki ; Dennis, Joe ; Tyrer, Jonathan P. ; Wilkinson, Jennifer S. ; Gómez-Caamaño, Antonio ; Tanteles, George A. ; Platte, Radka ; Mayes, Rebecca ; Conroy, Don ; Maranian, Mel ; Luccarini, Craig ; Gulliford, Sarah L. ; Sydes, Matthew R. ; Hall, Emma ; Haviland, Joanne ; Misra, Vivek ; Titley, Jennifer ; Bentzen, Søren M. ; Pharoah, Paul D P ; Burnet, Neil G. ; Dunning, Alison M. ; West, Catharine M L. / A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. In: Radiotherapy and Oncology. 2014 ; Vol. 111, No. 2. pp. 178-185.

Bibtex

@article{45c4d95f9bfd4b78b7707e612c705772,
title = "A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity",
abstract = "Background and purpose This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2 years after radiotherapy. Materials and methods A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Results Quantile-quantile plots show more associations at the P <5 × 10-7 level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. Conclusions This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable. {\circledC} 2014 Elsevier Ireland Ltd. All rights reserved.",
keywords = "Adverse effects, Genetics, Genome-wide association scan, Late toxicity, Radiotherapy",
author = "Barnett, {Gillian C.} and Deborah Thompson and Laura Fachal and Sarah Kerns and Chris Talbot and Elliott, {Rebecca M.} and Leila Dorling and Coles, {Charlotte E.} and Dearnaley, {David P.} and Rosenstein, {Barry S.} and Ana Vega and Paul Symonds and John Yarnold and Caroline Baynes and Kyriaki Michailidou and Joe Dennis and Tyrer, {Jonathan P.} and Wilkinson, {Jennifer S.} and Antonio G{\'o}mez-Caama{\~n}o and Tanteles, {George A.} and Radka Platte and Rebecca Mayes and Don Conroy and Mel Maranian and Craig Luccarini and Gulliford, {Sarah L.} and Sydes, {Matthew R.} and Emma Hall and Joanne Haviland and Vivek Misra and Jennifer Titley and Bentzen, {S{\o}ren M.} and Pharoah, {Paul D P} and Burnet, {Neil G.} and Dunning, {Alison M.} and West, {Catharine M L}",
note = ", Medical Research Council, United Kingdom",
year = "2014",
doi = "10.1016/j.radonc.2014.02.012",
language = "English",
volume = "111",
pages = "178--185",
journal = "Radiotherapy & Oncology",
issn = "0167-8140",
publisher = "Elsevier BV",
number = "2",

}

RIS

TY - JOUR

T1 - A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity

AU - Barnett, Gillian C.

AU - Thompson, Deborah

AU - Fachal, Laura

AU - Kerns, Sarah

AU - Talbot, Chris

AU - Elliott, Rebecca M.

AU - Dorling, Leila

AU - Coles, Charlotte E.

AU - Dearnaley, David P.

AU - Rosenstein, Barry S.

AU - Vega, Ana

AU - Symonds, Paul

AU - Yarnold, John

AU - Baynes, Caroline

AU - Michailidou, Kyriaki

AU - Dennis, Joe

AU - Tyrer, Jonathan P.

AU - Wilkinson, Jennifer S.

AU - Gómez-Caamaño, Antonio

AU - Tanteles, George A.

AU - Platte, Radka

AU - Mayes, Rebecca

AU - Conroy, Don

AU - Maranian, Mel

AU - Luccarini, Craig

AU - Gulliford, Sarah L.

AU - Sydes, Matthew R.

AU - Hall, Emma

AU - Haviland, Joanne

AU - Misra, Vivek

AU - Titley, Jennifer

AU - Bentzen, Søren M.

AU - Pharoah, Paul D P

AU - Burnet, Neil G.

AU - Dunning, Alison M.

AU - West, Catharine M L

N1 - , Medical Research Council, United Kingdom

PY - 2014

Y1 - 2014

N2 - Background and purpose This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2 years after radiotherapy. Materials and methods A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Results Quantile-quantile plots show more associations at the P <5 × 10-7 level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. Conclusions This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable. © 2014 Elsevier Ireland Ltd. All rights reserved.

AB - Background and purpose This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2 years after radiotherapy. Materials and methods A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Results Quantile-quantile plots show more associations at the P <5 × 10-7 level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. Conclusions This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable. © 2014 Elsevier Ireland Ltd. All rights reserved.

KW - Adverse effects

KW - Genetics

KW - Genome-wide association scan

KW - Late toxicity

KW - Radiotherapy

U2 - 10.1016/j.radonc.2014.02.012

DO - 10.1016/j.radonc.2014.02.012

M3 - Article

VL - 111

SP - 178

EP - 185

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

SN - 0167-8140

IS - 2

ER -