Association of a common genetic variant of the IGF1 gene with clinical outcome in patients with HER2-positive breast cancer.

Abstract

193 Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Circulating IGF1 levels may be linked with an increased risk of colorectal and breast cancer. Further, IGF1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, recently have been associated with a poor clinical outcome in patients with colorectal cancer. However, the influence of IGF1 SNPs on the prognosis of patients with breast cancer is unknown. Therefore, we aimed at investigating the influence of IGF1 tagging polymorphisms associated with IGF1 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 treated between 2000 and 2010 at the Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria. 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 IGF1 tagging polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678) were genotyped by SNaPshot assays. Results: Mean follow up period was 4.3 (± 2.5) years. Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.029). Concordantly, in univariate Cox regression analyses the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 2.87 [1.07 –7.70]; p = 0.036). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 2.86 [1.06 –7.71]; p = 0.038). Thus, our results are in concordance with a recent report that the same SNP is associated with poorer clinical outcome in colorectal cancer patients. Other investigated genetic variants of the IGF1 gene were not significantly associated with event-free survival (all p-values > 0.05). Conclusions: For the first time, our study investigates the influence of IGF1 tagging polymorphisms on the clinical outcome of HER2-positive breast cancer patients suggesting SNP rs2946834 as a predictor for reduced event-free survival.