title: Significant survival impact of MACC1 polymorphisms in HER2 positive breast cancer patients.
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.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, 9495 Triesen, Liechtenstein.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hubalek
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, 9495 Triesen, Liechtenstein.
authors.forename: Simone
authors.initials: S
authors.lastname: Geller-Rhomberg
authors.affiliation: 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.
authors.forename: Klaus
authors.initials: K
authors.lastname: Gasser
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.affiliation: 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.
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.affiliation: Studienzentrum Onkologie Ravensburg, 88212 Ravensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mueller-Holzner
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Chamson
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.affiliation: 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.
authors.forename: Alois H
authors.initials: AH
authors.lastname: Lang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; C544162:MACC1 protein, human
keywords: Breast neoplasms; MACC1; Polymorphism; Single nucleotide; Survival