Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 3, pp 491–498

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

  • Axel Muendlein
  • Alois H. Lang
  • Simone Geller-Rhomberg
  • Thomas Winder
  • Klaus Gasser
  • Heinz Drexel
  • Thomas Decker
  • Elisabeth Mueller-Holzner
  • Martina Chamson
  • Christian Marth
  • Michael Hubalek
Original Paper

DOI: 10.1007/s00432-012-1355-3

Cite this article as:
Muendlein, A., Lang, A.H., Geller-Rhomberg, S. et al. J Cancer Res Clin Oncol (2013) 139: 491. doi:10.1007/s00432-012-1355-3
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Abstract

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 [1.14–8.22]; 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.

Keywords

Breast cancerHER2Single nucleotide polymorphismsInsulin-like growth factor 1Biomarker

Supplementary material

432_2012_1355_MOESM1_ESM.pdf (6 kb)
Supplementary material 1 (PDF 6 kb)
432_2012_1355_MOESM2_ESM.pdf (6 kb)
Supplementary material 2 (PDF 6 kb)
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Supplementary material 3 (PDF 9 kb)
432_2012_1355_MOESM4_ESM.pdf (21 kb)
Supplementary material 4 (PDF 20 kb)
432_2012_1355_MOESM5_ESM.pdf (152 kb)
Supplementary material 5 (PDF 151 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • 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. 1.Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT)FeldkirchAustria
  2. 2.Department of Medicine and CardiologyAcademic Teaching Hospital FeldkirchFeldkirchAustria
  3. 3.Private University of the Principality of LiechtensteinTriesenPrincipality of Liechtenstein
  4. 4.Studienzentrum Onkologie RavensburgRavensburgGermany
  5. 5.Department of Obstetrics and GynecologyInnsbruck Medical UniversityInnsbruckAustria