Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate CancerCitation formats

  • Authors:
  • Sarah L Kerns
  • Leila Dorling
  • Laura Fachal
  • Søren Bentzen
  • Paul D P Pharoah
  • Daniel R Barnes
  • Antonio Gómez-Caamaño
  • Ana M Carballo
  • David P Dearnaley
  • Paula Peleteiro
  • Sarah L Gulliford
  • Emma Hall
  • Kyriaki Michailidou
  • Ángel Carracedo
  • Michael Sia
  • Richard Stock
  • Nelson N Stone
  • Matthew R Sydes
  • Jonathan P Tyrer
  • Shahana Ahmed
  • Matthew Parliament
  • Harry Ostrer
  • Barry S Rosenstein
  • Ana Vega
  • Neil G Burnet
  • Alison M Dunning
  • Gillian C Barnett
  • Catharine M L West
  • Radiogenomics Consortium

Standard

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer. / Kerns, Sarah L; Dorling, Leila; Fachal, Laura; Bentzen, Søren; Pharoah, Paul D P; Barnes, Daniel R; Gómez-Caamaño, Antonio; Carballo, Ana M; Dearnaley, David P; Peleteiro, Paula; Gulliford, Sarah L; Hall, Emma; Michailidou, Kyriaki; Carracedo, Ángel; Sia, Michael; Stock, Richard; Stone, Nelson N; Sydes, Matthew R; Tyrer, Jonathan P; Ahmed, Shahana; Parliament, Matthew; Ostrer, Harry; Rosenstein, Barry S; Vega, Ana; Burnet, Neil G; Dunning, Alison M; Barnett, Gillian C; West, Catharine M L; Radiogenomics Consortium.

In: EBioMedicine, Vol. 10, 08.2016, p. 150-163.

Research output: Contribution to journalArticle

Harvard

Kerns, SL, Dorling, L, Fachal, L, Bentzen, S, Pharoah, PDP, Barnes, DR, Gómez-Caamaño, A, Carballo, AM, Dearnaley, DP, Peleteiro, P, Gulliford, SL, Hall, E, Michailidou, K, Carracedo, Á, Sia, M, Stock, R, Stone, NN, Sydes, MR, Tyrer, JP, Ahmed, S, Parliament, M, Ostrer, H, Rosenstein, BS, Vega, A, Burnet, NG, Dunning, AM, Barnett, GC, West, CML & Radiogenomics Consortium 2016, 'Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer', EBioMedicine, vol. 10, pp. 150-163. https://doi.org/10.1016/j.ebiom.2016.07.022

APA

Kerns, S. L., Dorling, L., Fachal, L., Bentzen, S., Pharoah, P. D. P., Barnes, D. R., ... Radiogenomics Consortium (2016). Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer. EBioMedicine, 10, 150-163. https://doi.org/10.1016/j.ebiom.2016.07.022

Vancouver

Author

Kerns, Sarah L ; Dorling, Leila ; Fachal, Laura ; Bentzen, Søren ; Pharoah, Paul D P ; Barnes, Daniel R ; Gómez-Caamaño, Antonio ; Carballo, Ana M ; Dearnaley, David P ; Peleteiro, Paula ; Gulliford, Sarah L ; Hall, Emma ; Michailidou, Kyriaki ; Carracedo, Ángel ; Sia, Michael ; Stock, Richard ; Stone, Nelson N ; Sydes, Matthew R ; Tyrer, Jonathan P ; Ahmed, Shahana ; Parliament, Matthew ; Ostrer, Harry ; Rosenstein, Barry S ; Vega, Ana ; Burnet, Neil G ; Dunning, Alison M ; Barnett, Gillian C ; West, Catharine M L ; Radiogenomics Consortium. / Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer. In: EBioMedicine. 2016 ; Vol. 10. pp. 150-163.

Bibtex

@article{3a972193b6b544b19f0c82d02dc9afb0,
title = "Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer",
abstract = "Nearly 50{\%} of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95{\%} confidence interval [CI] 2.08–4.69, p-value 4.16 × 10− 8) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95{\%} CI 1.90–3.86, p-value = 3.21 × 10− 8). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.",
author = "Kerns, {Sarah L} and Leila Dorling and Laura Fachal and S{\o}ren Bentzen and Pharoah, {Paul D P} and Barnes, {Daniel R} and Antonio G{\'o}mez-Caama{\~n}o and Carballo, {Ana M} and Dearnaley, {David P} and Paula Peleteiro and Gulliford, {Sarah L} and Emma Hall and Kyriaki Michailidou and {\'A}ngel Carracedo and Michael Sia and Richard Stock and Stone, {Nelson N} and Sydes, {Matthew R} and Tyrer, {Jonathan P} and Shahana Ahmed and Matthew Parliament and Harry Ostrer and Rosenstein, {Barry S} and Ana Vega and Burnet, {Neil G} and Dunning, {Alison M} and Barnett, {Gillian C} and West, {Catharine M L} and {Radiogenomics Consortium}",
note = "Copyright {\circledC} 2016 The Ohio State University Wexner Medical Center. Published by Elsevier B.V. All rights reserved.",
year = "2016",
month = "8",
doi = "10.1016/j.ebiom.2016.07.022",
language = "English",
volume = "10",
pages = "150--163",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer

AU - Kerns, Sarah L

AU - Dorling, Leila

AU - Fachal, Laura

AU - Bentzen, Søren

AU - Pharoah, Paul D P

AU - Barnes, Daniel R

AU - Gómez-Caamaño, Antonio

AU - Carballo, Ana M

AU - Dearnaley, David P

AU - Peleteiro, Paula

AU - Gulliford, Sarah L

AU - Hall, Emma

AU - Michailidou, Kyriaki

AU - Carracedo, Ángel

AU - Sia, Michael

AU - Stock, Richard

AU - Stone, Nelson N

AU - Sydes, Matthew R

AU - Tyrer, Jonathan P

AU - Ahmed, Shahana

AU - Parliament, Matthew

AU - Ostrer, Harry

AU - Rosenstein, Barry S

AU - Vega, Ana

AU - Burnet, Neil G

AU - Dunning, Alison M

AU - Barnett, Gillian C

AU - West, Catharine M L

AU - Radiogenomics Consortium

N1 - Copyright © 2016 The Ohio State University Wexner Medical Center. Published by Elsevier B.V. All rights reserved.

PY - 2016/8

Y1 - 2016/8

N2 - Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08–4.69, p-value 4.16 × 10− 8) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90–3.86, p-value = 3.21 × 10− 8). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.

AB - Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08–4.69, p-value 4.16 × 10− 8) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90–3.86, p-value = 3.21 × 10− 8). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.

U2 - 10.1016/j.ebiom.2016.07.022

DO - 10.1016/j.ebiom.2016.07.022

M3 - Article

VL - 10

SP - 150

EP - 163

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -