title: Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer.
abstract: BACKGROUND
  Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC) prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP) studies on CRC prognosis.
  
  
  METHODS
  We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs) in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort).
  
  
  RESULTS
  Two SNPs in the 3' untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32-0.85 and HR = 0.64, 95% CI 0.42-0.99, for TT carriers). These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22-0.82 and HR = 0.46, 95% CI 0.25-0.83). Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were ~2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV) were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20-2.57; rs10420252, OR = 1.68, 95% CI 1.11-2.53); rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09-2.56 in a dominant model).
  
  
  CONCLUSIONS
  This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, 69120, Germany.
authors.forename: Jesus
authors.initials: J
authors.lastname: Lascorz
authors.forename: Melanie
authors.initials: M
authors.lastname: Bevier
authors.forename: Witigo V
authors.initials: WV
authors.lastname: Schönfels
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.forename: Heiko
authors.initials: H
authors.lastname: Aselmann
authors.forename: Jan
authors.initials: J
authors.lastname: Beckmann
authors.forename: Jan
authors.initials: J
authors.lastname: Egberts
authors.forename: Stephan
authors.initials: S
authors.lastname: Buch
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D016017:Odds Ratio; D010085:Oxidative Phosphorylation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C027208:ubiquinone-binding proteins; C513775:COX6B1 protein, human; D003576:Electron Transport Complex IV