title: A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients.
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.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment, A-6800 Feldkirch, Austria.
authors.forename: Alois H
authors.initials: AH
authors.lastname: Lang
authors.forename: Simone
authors.initials: S
authors.lastname: Geller-Rhomberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Winder
authors.forename: Nicole
authors.initials: N
authors.lastname: Stark
authors.forename: Klaus
authors.initials: K
authors.lastname: Gasser
authors.forename: Bernd
authors.initials: B
authors.lastname: Hartmann
authors.forename: Bertram
authors.initials: B
authors.lastname: Kohler
authors.forename: Ina
authors.initials: I
authors.lastname: Grizelj
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
mesh_terms: D000368:Aged; D001317:Austria / Q000453:epidemiology; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D016019:Survival Analysis; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors