TY - JOUR
T1 - Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity
AU - Barnett, Gillian C.
AU - Elliott, Rebecca M.
AU - Alsner, Jan
AU - Andreassen, Christian N.
AU - Abdelhay, Osama
AU - Burnet, Neil G.
AU - Chang-Claude, Jenny
AU - Coles, Charlotte E.
AU - Gutiérrez-Enríquez, Sara
AU - Fuentes-Raspall, Maria J.
AU - Alonso-Muñoz, Maria C.
AU - Kerns, Sarah
AU - Raabe, Annette
AU - Symonds, R. Paul
AU - Seibold, Petra
AU - Talbot, Chris J.
AU - Wenz, Frederik
AU - Wilkinson, Jennifer
AU - Yarnold, John
AU - Dunning, Alison M.
AU - Rosenstein, Barry S.
AU - West, Catharine M.L.
AU - Bentzen, Soren M.
N1 - Funding Information:
Dr. Gillian Barnett is funded the National Institute of Health Research (NIHR) and previously by a fellowship from Cancer Research UK and The Royal College of Radiologists [ C26900/A8740 ]. She also received funding from Addenbrooke’s Charitable Trust . Dr. Charlotte Coles and Prof. Neil Burnet are supported by the Cambridge NIHR Biomedical Research Centre. Dr. Alison Dunning is funded by Cancer Research UK [ C8197/A10865 ] and the Joseph Mitchell Trust . Prof. Catharine West is supported by Cancer Research UK and Experimental Cancer Medicine Centre (ECMC) funding. The collaborative group (RAPPER) is funded by Cancer Research UK. The LeND cohort was funded by a grant from the Breast Cancer Campaign to Prof. R. Paul Symonds and Dr. Chris Talbot. The MARIE study was funded in part by the Dietmar Hopp Stiftung and the Deutsche Krebshilfe e.V. (project numbers 108253 and 108419 ). Dr. Sara Gutiérrez-Enríquez was supported by a Grant of the “ Fondo de Investigación Sanitaria ” from the Spanish Health Ministry [ FIS 05/2181 ] and is currently funded by a Miguel Servet contract of the Instituto de Salud Carlos III . Prof. Barry Rosenstein and Dr. Sarah Kerns are funded by Grants RSGT-05-200-01-CCE from the American Cancer Society , PC074201 from the Department of Defense and 1R01CA134444 from the National Institutes of Health . The RACE study was funded by Cancer Research UK, and Prof. John Yarnold is supported by the Royal Marsden and ICR NIHR Biomedial Research Centre. Christian Nicolaj Andreassen and Jan Alsner received funding from the Danish Cancer Society , the Danish Council for Strategic Research , and CIRRO – The Lundbeck Foundation Centre for Interventional Research in Radiation Oncology . Prof. Soren Bentzen acknowledges support from the National Cancer Institute Grant No. 2P30 CA 014520.34 .
PY - 2012/12
Y1 - 2012/12
N2 - 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 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.
AB - 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 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.
KW - Adverse effects
KW - Meta-analysis
KW - Radiotherapy
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84871182048&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2012.10.017
DO - 10.1016/j.radonc.2012.10.017
M3 - Article
C2 - 23199655
AN - SCOPUS:84871182048
SN - 0167-8140
VL - 105
SP - 289
EP - 295
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 3
ER -