title: Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity.
abstract: OBJECTIVE
  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the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cambridge University Hospital NHS Foundation Trust, UK. gillbarnett@doctors.org.uk
authors.forename: Gillian C
authors.initials: GC
authors.lastname: Barnett
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Elliott
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.forename: Christian N
authors.initials: CN
authors.lastname: Andreassen
authors.forename: Osama
authors.initials: O
authors.lastname: Abdelhay
authors.forename: Neil G
authors.initials: NG
authors.lastname: Burnet
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Coles
authors.forename: Sara
authors.initials: S
authors.lastname: Gutiérrez-Enríquez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Fuentes-Raspall
authors.forename: Maria C
authors.initials: MC
authors.lastname: Alonso-Muñoz
authors.forename: Sarah
authors.initials: S
authors.lastname: Kerns
authors.forename: Annette
authors.initials: A
authors.lastname: Raabe
authors.forename: R Paul
authors.initials: RP
authors.lastname: Symonds
authors.forename: Petra
authors.initials: P
authors.lastname: Seibold
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Talbot
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilkinson
authors.forename: John
authors.initials: J
authors.lastname: Yarnold
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Barry S
authors.initials: BS
authors.lastname: Rosenstein
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D005355:Fibrosis / Q000209:etiology; D005838:Genotype; D006801:Humans; D016014:Linear Models; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011832:Radiation Injuries / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012306:Risk; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1