title: Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer.
abstract: OBJECTIVE
  Insulin-like growth factor 1 (IGF-1) stimulates mitosis and inhibits apoptosis. High circulating IGF-1 levels are linked with an increased risk of colorectal and breast cancer. Recently, IGF-1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, have been associated with poor clinical outcome in patients with colorectal cancer. In the present study, we aimed to investigate the influence of IGF1 polymorphisms associated with IGF-1 plasma levels on event-free survival in patients with HER2-positive breast cancer.
  
  
  METHODS
  The present study included 161 consecutive white patients with HER2-positive breast cancer. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin-embedded tumor tissue samples; five IGF-1 polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678), all associated with IGF-1 levels, were genotyped by SNaPshot assays.
  
  
  RESULTS
  Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.020). Concordantly, in univariate Cox regression analyses, the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 3.06 [1.14-8.22]; p = 0.027). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 4.02 [1.36-11.90]; p = 0.012). Other investigated polymorphisms of the IGF1 gene were not significantly associated with event-free survival (all p values >0.05).
  
  
  CONCLUSIONS
  This study provides first evidence that IGF1 rs2946834 polymorphism is associated with clinical outcome of HER2-positive breast cancer patients. Further studies are warranted to validate these findings.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, Carinagasse 47, 6800 Feldkirch, Austria. axel.muendlein@vivit.at
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.forename: Alois H
authors.initials: AH
authors.lastname: Lang
authors.forename: Simone
authors.initials: S
authors.lastname: Geller-Rhomberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.forename: Klaus
authors.initials: K
authors.lastname: Gasser
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mueller-Holzner
authors.forename: Martina
authors.initials: M
authors.lastname: Chamson
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Michael
authors.initials: M
authors.lastname: Hubalek
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D007334:Insulin-Like Growth Factor I; D018719:Erb-b2 Receptor Tyrosine Kinases