TY - JOUR
T1 - 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
AU - Andreassen, Christian Nicolaj
AU - Rosenstein, Barry S.
AU - Kerns, Sarah L.
AU - Ostrer, Harry
AU - De Ruysscher, Dirk
AU - Cesaretti, Jamie A.
AU - Barnett, Gillian C.
AU - Dunning, Alison M.
AU - Dorling, Leila
AU - West, Catharine M. L.
AU - Burnet, Neil G.
AU - Elliott, Rebecca
AU - Coles, Charlotte
AU - Hall, Emma
AU - Fachal, Laura
AU - Vega, Ana
AU - Gomez-Caamano, Antonio
AU - Talbot, Christopher J.
AU - Symonds, R. Paul
AU - De Ruyck, Kim
AU - Thierens, Hubert
AU - Ost, Piet
AU - Chang-Claude, Jenny
AU - Seibold, Petra
AU - Popanda, Odilia
AU - Overgaard, Marie
AU - Dearnaley, David
AU - Sydes, Matthew R.
AU - Azria, David
AU - Koch, Christine Anne
AU - Parliament, Matthew
AU - Blackshaw, Michael
AU - Sia, Michael
AU - Fuentes-Raspall, Maria J.
AU - Ramon y Cajal, Teresa
AU - Barnadas, Agustin
AU - Vesprini, Danny
AU - Gutierrez-Enriquez, Sara
AU - Molla, Meritxell
AU - Diez, Orland
AU - Yarnold, John R.
AU - Overgaard, Jens
AU - Bentzen, Soren M.
AU - Alsner, Jan
PY - 2016/12
Y1 - 2016/12
N2 - Purpose: Several small studies have indicated that the ATM rsl 801516 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.
AB - Purpose: Several small studies have indicated that the ATM rsl 801516 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.
KW - Normal tissue toxicity
KW - Radiosensitivity
KW - Ataxia telangiectasia mutated
KW - p.Asp1853Asn
KW - c.5557G > A
U2 - 10.1016/j.radonc.2016.06.017
DO - 10.1016/j.radonc.2016.06.017
M3 - Article
SN - 0167-8140
VL - 121
SP - 431
EP - 439
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 3
ER -