Journal
RADIOTHERAPY AND ONCOLOGY
Volume 105, Issue 3, Pages 289-295Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2012.10.017
Keywords
Meta-analysis; Radiotherapy; Toxicity; Adverse effects
Funding
- National Institute of Health Research (NIHR)
- Cancer Research UK
- Royal College of Radiologists [C26900/A8740]
- Addenbrooke's Charitable Trust
- Cambridge NIHR Biomedical Research Centre
- Cancer Research UK [C8197/A10865]
- Joseph Mitchell Trust
- Experimental Cancer Medicine Centre (ECMC)
- Breast Cancer Campaign
- Dietmar Hopp Stiftung
- Deutsche Krebshilfe e.V. [108253, 108419]
- Spanish Health Ministry [FIS 05/2181]
- Instituto de Salud Carlos III
- American Cancer Society [RSGT-05-200-01-CCE]
- Department of Defense [PC074201]
- National Institutes of Health [1R01CA134444]
- Royal Marsden
- ICR NIHR Biomedial Research Centre
- Danish Cancer Society
- Danish Council for Strategic Research
- CIRRO - The Lundbeck Foundation Centre for Interventional Research in Radiation Oncology
- National Cancer Institute [2P30 CA 014520.34]
- Medical Research Council [G9600656] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10026] Funding Source: researchfish
- MRC [G9600656] Funding Source: UKRI
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Background and purpose: Reported associations between risk of radiation-induced normal tissue injury and single nucleotide polymorphisms (SNPs) in TGFB1, encoding the pro-fibrotic cytokine transforming growth factor-beta 1 (TGF-beta 1), remain controversial. To overcome publication bias, the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies. Materials and methods: TGFB1 SNP rs1800469 c.-1347T>C (previously known as C-509T) genotype, treatment-related data, and clinically-assessed fibrosis (measured at least 2 years after therapy) were available in 2782 participants from 11 cohorts. All received adjuvant breast radiotherapy. Associations between late fibrosis or overall toxicity, reported by STAT (Standardised Total Average Toxicity) score, and rs1800469 genotype were assessed. Results: No statistically significant associations between either fibrosis or overall toxicity and rs1800469 genotype were observed with univariate or multivariate regression analysis. The multivariate odds ratio (OR), obtained from meta-analysis, for an increase in late fibrosis grade with each additional rare allele of rs1800469 was 0.98 (95% Confidence Interval (CI) 0.85-1.11). This CI is sufficiently narrow to rule out any clinically relevant effect on toxicity risk in carriers vs. non-carriers with a high probability. Conclusion: This meta-analysis has not confirmed previous reports. of association between fibrosis or overall toxicity and rs1800469 genotype in breast cancer patients. It has demonstrated successful collaboration within the Radiogenomics Consortium. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 289-295
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