Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer

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• 作者：Axel Muendlein (1) (3)
  Alois H. Lang (1) (2)
  Simone Geller-Rhomberg (1) (3)
  Thomas Winder (1) (2) (3)
  Klaus Gasser (1) (2) (3)
  Heinz Drexel (1) (2) (3)
  Thomas Decker (4)
  Elisabeth Mueller-Holzner (5)
  Martina Chamson (5)
  Christian Marth (5)
  Michael Hubalek (5)
  
• 关键词：Breast cancer ; HER2 ; Single nucleotide polymorphisms ; Insulin ; like growth factor 1 ; Biomarker
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：139
• 期：3
• 页码：491-498
• 全文大小：212KB
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• 作者单位：Axel Muendlein (1) (3)
  Alois H. Lang (1) (2)
  Simone Geller-Rhomberg (1) (3)
  Thomas Winder (1) (2) (3)
  Klaus Gasser (1) (2) (3)
  Heinz Drexel (1) (2) (3)
  Thomas Decker (4)
  Elisabeth Mueller-Holzner (5)
  Martina Chamson (5)
  Christian Marth (5)
  Michael Hubalek (5)
  
  1. Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, 6800, Feldkirch, Austria
  3. Private University of the Principality of Liechtenstein, 9495, Triesen, Principality of Liechtenstein
  2. Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, 6800, Feldkirch, Austria
  4. Studienzentrum Onkologie Ravensburg, 88212, Ravensburg, Germany
  5. Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020, Innsbruck, Austria
  
• ISSN：1432-1335

文摘

Purpose 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-.22]; p?=?0.027). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR?=?4.02 [1.36-1.90]; 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.