Faculty Collaboration Database

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. Radiother Oncol 2016 Dec;121(3):431-439

Date

07/23/2016

Pubmed ID

27443449

Pubmed Central ID

PMC5559879

DOI

10.1016/j.radonc.2016.06.017

Scopus ID

2-s2.0-84997428777 (requires institutional sign-in at Scopus site)   88 Citations

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.

Author List

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)

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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