Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity
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-β1), remain controversial. To overcome publication bias, the internation...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 2012
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| In: |
Radiotherapy and oncology
Year: 2012, Volume: 105, Issue: 3, Pages: 289-295 |
| ISSN: | 1879-0887 |
| DOI: | 10.1016/j.radonc.2012.10.017 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.radonc.2012.10.017 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0167814012004744 
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| Author Notes: | Gillian C. Barnett, Rebecca M. Elliott, Jan Alsner, Christian N. Andreassen, Osama Abdelhay, Neil G. Burnet, Jenny Chang-Claude, Charlotte E. Coles, Sara Gutiérrez-Enríquez, Maria J. Fuentes-Raspall, Maria C. Alonso-Muñoz, Sarah Kerns, Annette Raabe, R. Paul Symonds, Petra Seibold, Chris J. Talbot, Frederik Wenz, Jennifer Wilkinson, John Yarnold, Alison M. Dunning, Barry S. Rosenstein, Catharine M. L. West, Søren M. Bentzen |
| Summary: | 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-β1), 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the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies.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 2years 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. |
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| Item Description: | Available online 28 November 2012 Gesehen am 23.10.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0887 |
| DOI: | 10.1016/j.radonc.2012.10.017 |