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.


Type
Article
Change log
Authors
Andreassen, Christian Nicolaj 
Rosenstein, Barry S 
Kerns, Sarah L 
Ostrer, Harry 
De Ruysscher, Dirk 
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.

Description
Keywords
Ataxia telangiectasia mutated, Normal tissue toxicity, Radiosensitivity, c.5557G>A, p.Asp1853Asn, Alleles, Ataxia Telangiectasia Mutated Proteins, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genotype, Heterozygote, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Radiation Injuries, Radiation Tolerance, Radiotherapy, Risk Factors
Journal Title
Radiother Oncol
Conference Name
Journal ISSN
0167-8140
1879-0887
Volume Title
121
Publisher
Elsevier BV
Sponsorship
Cancer Research Uk (None)