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.
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Date
2016-12-01Author
Andreassen, CN
Rosenstein, BS
Kerns, SL
Ostrer, H
De Ruysscher, D
Cesaretti, JA
Barnett, GC
Dunning, AM
Dorling, L
West, CML
Burnet, NG
Elliott, R
Coles, C
Hall, E
Fachal, L
Vega, A
Gómez-Caamaño, A
Talbot, CJ
Symonds, RP
De Ruyck, K
Thierens, H
Ost, P
Chang-Claude, J
Seibold, P
Popanda, O
Overgaard, M
Dearnaley, D
Sydes, MR
Azria, D
Koch, CA
Parliament, M
Blackshaw, M
Sia, M
Fuentes-Raspall, MJ
Ramon Y Cajal, T
Barnadas, A
Vesprini, D
Gutiérrez-Enríquez, S
Mollà, M
Díez, O
Yarnold, JR
Overgaard, J
Bentzen, SM
Alsner, J
International Radiogenomics Consortium (RgC),
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
International Radiogenomics Consortium (RgC)
Humans
Breast Neoplasms
Prostatic Neoplasms
Radiation Injuries
Genetic Predisposition to Disease
Radiotherapy
Odds Ratio
Risk Factors
Genotype
Heterozygote
Polymorphism, Single Nucleotide
Alleles
Radiation Tolerance
Middle Aged
Female
Male
Ataxia Telangiectasia Mutated Proteins
Research team
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Dearnaley)
Language
eng
Date accepted
2016-06-29
License start date
2016-12
Citation
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2016, 121 (3), pp. 431 - 439
Publisher
ELSEVIER IRELAND LTD