Article open access publication

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

Radiotherapy and Oncology, Elsevier, ISSN 1879-0887

Volume 121, 3, 2016

DOI:10.1016/j.radonc.2016.06.017, Dimensions: pub.1031268305, PMC: PMC5559879, PMID: 27443449,

Affiliations

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  1. (1) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  2. (2) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  3. (3) University of Rochester Medical Center, grid.412750.5
  4. (4) Albert Einstein College of Medicine, grid.251993.5
  5. (5) Maastricht University Medical Centre, grid.412966.e
  6. (6) Southpoint Cancer Center, Jacksonville, USA
  7. (7) Cambridge University Hospitals NHS Foundation Trust, grid.24029.3d
  8. (8) University of Cambridge, grid.5335.0
  9. (9) Institute of Cancer Sciences, University of Manchester, The Christie NHS Foundation Trust, UK
  10. (10) Institute of Cancer Research, grid.18886.3f
  11. (11) Fundacion Publica Galega de Medicina Xenomica-SERGAS, Grupo de Medicina Xenomica-USC, IDIS, CIBERER, Santiago de Compostela, Spain
  12. (12) Complejo Hospitalario Universitario de Santiago, grid.411048.8
  13. (13) University of Leicester, grid.9918.9
  14. (14) Ghent University, grid.5342.0
  15. (15) Ghent University Hospital, grid.410566.0
  16. (16) University Cancer Center Hamburg, grid.412315.0
  17. (17) German Cancer Research Center, grid.7497.d
  18. (18) MRC Clinical Trials Unit, grid.415052.7
  19. (19) UniCancer Group, grid.418189.d
  20. (20) Princess Margaret Cancer Centre, grid.415224.4
  21. (21) University of Alberta, grid.17089.37
  22. (22) Department of Radiation Oncology, British Columbia Cancer Agency Abbotsford Clinic, Canada
  23. (23) Hospital de Sant Pau, grid.413396.a
  24. (24) Sunnybrook Health Science Centre, grid.413104.3
  25. (25) Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Spain
  26. (26) Hospital Universitari Vall d'Hebron, grid.411083.f
  27. (27) University of Maryland, Baltimore, grid.411024.2

Description

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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Aarhus University

Danish Open Access Indicator

2016: Unused

Research area: Medicine

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2016: Level 1

Research area: Medicine

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Times Cited: 49

Field Citation Ratio (FCR): 12.76

Relative Citation ratio (RCR): 2.6

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