A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

doi:10.1186/1471-2407-12-20

BMC Cancer. 2012; 12: 20.

Published online 2012 January 17. doi: 10.1186/1471-2407-12-20

PMCID: PMC3282635

A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

Alois H Lang,^#^1,² Simone Geller-Rhomberg,^#^1,³ Thomas Winder,^1,^2,³ Nicole Stark,^1,³ Klaus Gasser,^1,^2,³ Bernd Hartmann,² Bertram Kohler,² Ina Grizelj,¹ Heinz Drexel,^1,^2,^3,⁴ and Axel Muendlein^1,³

¹Vorarlberg Institute for Vascular Investigation and Treatment, A-6800 Feldkirch, Austria

²Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, A-6800 Feldkirch, Austria

³Private University of the Principality of Liechtenstein, FL-9495 Triesen, Principality of Liechtenstein

⁴Drexel University College of Medicine, Philadelphia, PA 19104, USA

Corresponding author.

^#Contributed equally.

Alois H Lang: alois.lang/at/lkhf.at; Simone Geller-Rhomberg: simone.rhomberg/at/vivit.at; Thomas Winder: thomas.winder/at/lkhf.at; Nicole Stark: nicole.stark/at/vivit.at; Klaus Gasser: klaus.gasser/at/vivit.at; Bernd Hartmann: bernd.hartmann/at/lkhf.at; Bertram Kohler: bertram.kohler/at/lkhf.at; Ina Grizelj: inagri/at/gmx.at; Heinz Drexel: vivit/at/lkhf.at; Axel Muendlein: axel.muendlein/at/vivit.at

Received July 20, 2011; Accepted January 17, 2012.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.

Abstract

Background

The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.

Methods

The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.

Results

Over a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05).

Conclusions

For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.

Articles from BMC Cancer are provided here courtesy of
BioMed Central