Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.Citation formats

  • External authors:
  • Mahbubl Ahmed
  • Leila Dorling
  • Sarah Kerns
  • Laura Fachal
  • Matt Partliament
  • Barry S Rosenstein
  • Ana Vega
  • Antonio Gómez-Caamaño
  • Gill Barnett
  • David P Dearnaley
  • Emma Hall
  • Matt Sydes
  • Neil Burnet
  • Paul D P Pharoah
  • Ros Eeles

Standard

Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity. / Ahmed, Mahbubl; Dorling, Leila; Kerns, Sarah; Fachal, Laura; Elliott, Rebecca; Partliament, Matt; Rosenstein, Barry S; Vega, Ana; Gómez-Caamaño, Antonio; Barnett, Gill; Dearnaley, David P; Hall, Emma; Sydes, Matt; Burnet, Neil; Pharoah, Paul D P; Eeles, Ros; West, Catharine M L.

In: Br J Cancer, Vol. 114, No. 10, 10.05.2016, p. 1165-74.

Research output: Contribution to journalArticlepeer-review

Harvard

Ahmed, M, Dorling, L, Kerns, S, Fachal, L, Elliott, R, Partliament, M, Rosenstein, BS, Vega, A, Gómez-Caamaño, A, Barnett, G, Dearnaley, DP, Hall, E, Sydes, M, Burnet, N, Pharoah, PDP, Eeles, R & West, CML 2016, 'Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.', Br J Cancer, vol. 114, no. 10, pp. 1165-74. https://doi.org/10.1038/bjc.2016.94

APA

Ahmed, M., Dorling, L., Kerns, S., Fachal, L., Elliott, R., Partliament, M., Rosenstein, B. S., Vega, A., Gómez-Caamaño, A., Barnett, G., Dearnaley, D. P., Hall, E., Sydes, M., Burnet, N., Pharoah, P. D. P., Eeles, R., & West, C. M. L. (2016). Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity. Br J Cancer, 114(10), 1165-74. https://doi.org/10.1038/bjc.2016.94

Vancouver

Author

Ahmed, Mahbubl ; Dorling, Leila ; Kerns, Sarah ; Fachal, Laura ; Elliott, Rebecca ; Partliament, Matt ; Rosenstein, Barry S ; Vega, Ana ; Gómez-Caamaño, Antonio ; Barnett, Gill ; Dearnaley, David P ; Hall, Emma ; Sydes, Matt ; Burnet, Neil ; Pharoah, Paul D P ; Eeles, Ros ; West, Catharine M L. / Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity. In: Br J Cancer. 2016 ; Vol. 114, No. 10. pp. 1165-74.

Bibtex

@article{a2e82c44580e4763928c605e97813509,
title = "Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.",
abstract = "BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy.METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods.RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity.CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens.",
keywords = "Aged, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Principal Component Analysis, Prostatic Neoplasms, Radiation Injuries, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.",
author = "Mahbubl Ahmed and Leila Dorling and Sarah Kerns and Laura Fachal and Rebecca Elliott and Matt Partliament and Rosenstein, {Barry S} and Ana Vega and Antonio G{\'o}mez-Caama{\~n}o and Gill Barnett and Dearnaley, {David P} and Emma Hall and Matt Sydes and Neil Burnet and Pharoah, {Paul D P} and Ros Eeles and West, {Catharine M L}",
year = "2016",
month = may,
day = "10",
doi = "10.1038/bjc.2016.94",
language = "English",
volume = "114",
pages = "1165--74",
journal = "BJC",
issn = "0007-0920",
publisher = "Springer Nature",
number = "10",

}

RIS

TY - JOUR

T1 - Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.

AU - Ahmed, Mahbubl

AU - Dorling, Leila

AU - Kerns, Sarah

AU - Fachal, Laura

AU - Elliott, Rebecca

AU - Partliament, Matt

AU - Rosenstein, Barry S

AU - Vega, Ana

AU - Gómez-Caamaño, Antonio

AU - Barnett, Gill

AU - Dearnaley, David P

AU - Hall, Emma

AU - Sydes, Matt

AU - Burnet, Neil

AU - Pharoah, Paul D P

AU - Eeles, Ros

AU - West, Catharine M L

PY - 2016/5/10

Y1 - 2016/5/10

N2 - BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy.METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods.RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity.CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens.

AB - BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy.METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods.RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity.CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens.

KW - Aged

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Germ-Line Mutation

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Principal Component Analysis

KW - Prostatic Neoplasms

KW - Radiation Injuries

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1038/bjc.2016.94

DO - 10.1038/bjc.2016.94

M3 - Article

C2 - 27070714

VL - 114

SP - 1165

EP - 1174

JO - BJC

JF - BJC

SN - 0007-0920

IS - 10

ER -