Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

International Radiogenomics Consortium (RgC)

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. Materials and methods The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. Results For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. Conclusion This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalRadiotherapy and Oncology
Volume121
Issue number3
DOIs
StatePublished - Dec 1 2016

Fingerprint

Single Nucleotide Polymorphism
Meta-Analysis
Prostatic Neoplasms
Radiotherapy
Breast Neoplasms
Alleles
Telangiectasis
Inheritance Patterns
Fibrosis
Odds Ratio
Radiation
Skin
Therapeutics

Keywords

  • Ataxia telangiectasia mutated
  • c.5557G>A
  • Normal tissue toxicity
  • p.Asp1853Asn
  • Radiosensitivity

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients. / International Radiogenomics Consortium (RgC).

In: Radiotherapy and Oncology, Vol. 121, No. 3, 01.12.2016, p. 431-439.

Research output: Contribution to journalArticle

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title = "Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients",
abstract = "Purpose Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. Materials and methods The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. Results For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. Conclusion This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.",
keywords = "Ataxia telangiectasia mutated, c.5557G>A, Normal tissue toxicity, p.Asp1853Asn, Radiosensitivity",
author = "{International Radiogenomics Consortium (RgC)} and Andreassen, {Christian Nicolaj} and Rosenstein, {Barry S.} and Kerns, {Sarah L.} and Harry Ostrer and {De Ruysscher}, Dirk and Cesaretti, {Jamie A.} and Barnett, {Gillian C.} and Dunning, {Alison M.} and Leila Dorling and West, {Catharine M L} and Burnet, {Neil G.} and Rebecca Elliott and Charlotte Coles and Emma Hall and Laura Fachal and Ana Vega and Antonio G{\'o}mez-Caama{\~n}o and Talbot, {Christopher J.} and Symonds, {R. Paul} and {De Ruyck}, Kim and Hubert Thierens and Piet Ost and Jenny Chang-Claude and Petra Seibold and Odilia Popanda and Marie Overgaard and David Dearnaley and Sydes, {Matthew R.} and David Azria and Koch, {Christine Anne} and Matthew Parliament and Michael Blackshaw and Michael Sia and Fuentes-Raspall, {Maria J.} and {Ramon y Cajal}, Teresa and Agustin Barnadas and Danny Vesprini and Sara Guti{\'e}rrez-Enr{\'i}quez and Meritxell Moll{\`a} and Orland D{\'i}ez and Yarnold, {John R.} and Jens Overgaard and Bentzen, {S{\o}ren M.} and Jan Alsner",
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T1 - Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

AU - International Radiogenomics Consortium (RgC)

AU - Andreassen, Christian Nicolaj

AU - Rosenstein, Barry S.

AU - Kerns, Sarah L.

AU - Ostrer, Harry

AU - De Ruysscher, Dirk

AU - Cesaretti, Jamie A.

AU - Barnett, Gillian C.

AU - Dunning, Alison M.

AU - Dorling, Leila

AU - West, Catharine M L

AU - Burnet, Neil G.

AU - Elliott, Rebecca

AU - Coles, Charlotte

AU - Hall, Emma

AU - Fachal, Laura

AU - Vega, Ana

AU - Gómez-Caamaño, Antonio

AU - Talbot, Christopher J.

AU - Symonds, R. Paul

AU - De Ruyck, Kim

AU - Thierens, Hubert

AU - Ost, Piet

AU - Chang-Claude, Jenny

AU - Seibold, Petra

AU - Popanda, Odilia

AU - Overgaard, Marie

AU - Dearnaley, David

AU - Sydes, Matthew R.

AU - Azria, David

AU - Koch, Christine Anne

AU - Parliament, Matthew

AU - Blackshaw, Michael

AU - Sia, Michael

AU - Fuentes-Raspall, Maria J.

AU - Ramon y Cajal, Teresa

AU - Barnadas, Agustin

AU - Vesprini, Danny

AU - Gutiérrez-Enríquez, Sara

AU - Mollà, Meritxell

AU - Díez, Orland

AU - Yarnold, John R.

AU - Overgaard, Jens

AU - Bentzen, Søren M.

AU - Alsner, Jan

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. Materials and methods The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. Results For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. Conclusion This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

AB - Purpose Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium. Materials and methods The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity. Results For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance. Conclusion This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.

KW - Ataxia telangiectasia mutated

KW - c.5557G>A

KW - Normal tissue toxicity

KW - p.Asp1853Asn

KW - Radiosensitivity

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SN - 0167-8140

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