期刊
RADIOTHERAPY AND ONCOLOGY
卷 121, 期 3, 页码 431-439出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2016.06.017
关键词
Normal tissue toxicity; Radiosensitivity; Ataxia telangiectasia mutated; p.Asp1853Asn; c.5557G > A
资金
- Danish Cancer Society
- NHS
- Cancer Research UK (CRUK) [C8197/A16565]
- UK Medical Research Council
- Cambridge National Institute of Health Research Biomedical Research Centre
- Instituto de Salud Carlos III (ISCIII) grant FIS [PI05/2181]
- Miguel Servet contract - ISCIII of the 'Ministerio Espanol de Economia y Competitividad'
- Institute de Salud Carlos III (FIS) [PI10/00164, PI13/02030]
- Fondo Europeo de Desarrollo Regional (FEDER)
- Xunta de Galicia
- European Social Fund [POS-A/2013/034]
- National Institutes of Health [1R01CA134444]
- Department of Defense [PC074201, PC140371]
- American Cancer Society [RSGT-05-200-01-CCE]
- Cancer Research UK
- Experimental Cancer Centre
- MRC [MC_UU_12023/28, MC_U122861330, MC_UU_12023/6] Funding Source: UKRI
- Cancer Research UK [10588, 16565, 18504, 7253, 19727] Funding Source: researchfish
- Medical Research Council [MC_UU_12023/6, MC_U122861330, 1366822, MC_UU_12023/28] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10106, NF-SI-0510-10026] Funding Source: researchfish
- The Danish Cancer Society [R72-A4448] Funding Source: researchfish
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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