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

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.

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Acknowledgments

We are grateful to Wera Hofmann (GATC Biotech, Konstanz, Germany), Bernd Hartmann (Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Austria), and Hans-Christian Fricke (Department of Obstetrics and Gynecology, Klinikum Konstanz, Germany) for their helpful and constructive comments on this manuscript. The present study was part financed by the European Union’s European Regional Development Fund through the INTERREG IV Program “Alpenrhein-Bodensee-Hochrhein”; Project Number: 179.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Correspondence to Axel Muendlein.

Additional information

Axel Muendlein and Alois H. Lang contributed equally to this work.

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Muendlein, A., Lang, A.H., Geller-Rhomberg, S. et al. Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer. J Cancer Res Clin Oncol 139, 491–498 (2013). https://doi.org/10.1007/s00432-012-1355-3

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Keywords

  • Breast cancer
  • HER2
  • Single nucleotide polymorphisms
  • Insulin-like growth factor 1
  • Biomarker