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: Axel Muendlein, Michael Hubalek, Simone Geller-Rhomberg, Klaus Gasser, Thomas Winder, Heinz Drexel, Thomas Decker, Elisabeth Mueller-Holzner, Martina Chamson, Christian Marth, Alois H Lang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 50 Issue 12 Pg. 2134-41 (Aug 2014) ISSN: 1879-0852 [Electronic] England
• PMID: 24910416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• MACC1 protein, human
• Trans-Activators
• Transcription Factors
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Breast Neoplasms (genetics, metabolism, mortality)
• Female
• Genotype
• Humans
• Middle Aged
• Multivariate Analysis
• Polymorphism, Single Nucleotide
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Survival Analysis
• Trans-Activators
• Transcription Factors (genetics)