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.
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.
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).
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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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.
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
- Breast cancer
- Single nucleotide polymorphisms
- Insulin-like growth factor 1