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Meta-Analysis
. 2016 Dec;121(3):431-439.
doi: 10.1016/j.radonc.2016.06.017. Epub 2016 Jul 18.

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

Christian Nicolaj Andreassen  1 , Barry S Rosenstein  2 , Sarah L Kerns  3 , Harry Ostrer  4 , Dirk De Ruysscher  5 , Jamie A Cesaretti  6 , Gillian C Barnett  7 , Alison M Dunning  7 , Leila Dorling  8 , Catharine M L West  9 , Neil G Burnet  10 , Rebecca Elliott  10 , Charlotte Coles  10 , Emma Hall  11 , Laura Fachal  12 , Ana Vega  12 , Antonio Gómez-Caamaño  13 , Christopher J Talbot  14 , R Paul Symonds  15 , Kim De Ruyck  16 , Hubert Thierens  16 , Piet Ost  17 , Jenny Chang-Claude  18 , Petra Seibold  19 , Odilia Popanda  20 , Marie Overgaard  21 , David Dearnaley  22 , Matthew R Sydes  23 , David Azria  24 , Christine Anne Koch  25 , Matthew Parliament  26 , Michael Blackshaw  26 , Michael Sia  27 , Maria J Fuentes-Raspall  28 , Teresa Ramon Y Cajal  29 , Agustin Barnadas  29 , Danny Vesprini  30 , Sara Gutiérrez-Enríquez  31 , Meritxell Mollà  32 , Orland Díez  33 , John R Yarnold  22 , Jens Overgaard  21 , Søren M Bentzen  34 , Jan Alsner  21 ; International Radiogenomics Consortium (RgC)
Affiliations
Meta-Analysis

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

Christian Nicolaj Andreassen et al. Radiother Oncol. 2016 Dec.

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; Normal tissue toxicity; Radiosensitivity; c.5557G>A; p.Asp1853Asn.

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Conflict of interest statement

Conflicts of interest: None.

Figures

Fig. 1
Fig. 1
Mean Z STAT and Z scores as per genotype for the eight normal tissue endpoints. Error bars indicate standard error of the mean (SEM).
Fig. 2
Fig. 2
Forest plot and funnel plot showing the meta-analysis result for having a Z STAT global score in the upper quartile (Asp/Asp and Asp/Asn vs. Asn/Asn).
Fig. 3
Fig. 3
Forest plot and funnel plot showing the meta-analysis result for having an R-STAT global score in the upper quartile (Asp/Asp and Asp/Asn vs. Asn/Asn).
See this image and copyright information in PMC

References

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