Axel Muendlein1, Michael Hubalek2, Simone Geller-Rhomberg1, Klaus Gasser3, Thomas Winder3, Heinz Drexel3, Thomas Decker4, Elisabeth Mueller-Holzner2, Martina Chamson2, Christian Marth2, Alois H Lang5. 1. Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, 9495 Triesen, Liechtenstein. 2. Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria. 3. Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, 9495 Triesen, Liechtenstein. 4. Studienzentrum Onkologie Ravensburg, 88212 Ravensburg, Germany. 5. Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria. Electronic address: alois.lang@lkhf.at.
Abstract
BACKGROUND: Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signalling has been associated with poor clinical outcome in breast cancer and other cancers. The recently discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Potential links between genetic variants of the MACC1 gene and survival in breast cancer patients are unknown. In the present study, we therefore aimed to investigate the influence of MACC1 polymorphisms on event-free and overall survival in patients with human epidermal growth factor 2 (HER2)-positive breast cancer. METHODS: The present study included 164 consecutive white patients with HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and rs3735615, already associated with cancer prognosis or with potential functional effects, were genotyped by the 5' nuclease assay. RESULTS: Multivariate Cox regression analysis adjusted for age and tumour stage showed increased risk for progression or death for carriers of the rare allele (G-allele) of single nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively). In addition, we were able to demonstrate an adverse effect on cancer prognosis for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007 and HR = 2.80; p = 0.003 for event-free survival and overall survival, respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant protective impact on event-free survival as well as overall survival (HR = 0.25; p = 0.001, and HR = 0.16; p = 0.001, respectively). CONCLUSIONS: This study provides first evidence that MACC1 polymorphisms are associated with clinical outcome for HER2-positive breast cancer patients. Further studies are warranted to validate these findings.
BACKGROUND: Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signalling has been associated with poor clinical outcome in breast cancer and other cancers. The recently discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Potential links between genetic variants of the MACC1 gene and survival in breast cancerpatients are unknown. In the present study, we therefore aimed to investigate the influence of MACC1 polymorphisms on event-free and overall survival in patients with human epidermal growth factor 2 (HER2)-positive breast cancer. METHODS: The present study included 164 consecutive white patients with HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and rs3735615, already associated with cancer prognosis or with potential functional effects, were genotyped by the 5' nuclease assay. RESULTS: Multivariate Cox regression analysis adjusted for age and tumour stage showed increased risk for progression or death for carriers of the rare allele (G-allele) of single nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively). In addition, we were able to demonstrate an adverse effect on cancer prognosis for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007 and HR = 2.80; p = 0.003 for event-free survival and overall survival, respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant protective impact on event-free survival as well as overall survival (HR = 0.25; p = 0.001, and HR = 0.16; p = 0.001, respectively). CONCLUSIONS: This study provides first evidence that MACC1 polymorphisms are associated with clinical outcome for HER2-positive breast cancerpatients. Further studies are warranted to validate these findings.
Authors: Viktor H Koelzer; Pia Herrmann; Inti Zlobec; Eva Karamitopoulou; Alessandro Lugli; Ulrike Stein Journal: BMC Cancer Date: 2015-03-21 Impact factor: 4.430
Authors: F Du; P Yuan; Z T Zhao; Z Yang; T Wang; J D Zhao; Y Luo; F Ma; J Y Wang; Y Fan; R G Cai; P Zhang; Q Li; Y M Song; B H Xu Journal: Sci Rep Date: 2016-09-21 Impact factor: 4.379