title: Mitochondrial DNA polymorphisms, its copy number change and outcome in colorectal cancer.
abstract: BACKGROUND
  Mitochondrion is a small organelle inside the eukaryotic cells. It has its own genome (mtDNA) and encodes for proteins that are critical for energy production and cellular metabolism. Mitochondrial dysfunctions have been implicated in cancer progression and may be related to poor prognosis in cancer patients. In this study we hypothesized that genetic variations in mtDNA are associated with clinical outcome in colorectal cancer patients.
  
  
  METHODS
  We tested the associations of six mtDNA polymorphisms [MitoT479C, MitoT491C, MitoT10035C, MitoA13781G, 10398 (A/G), and 16189 (T/C)] and the mtDNA copy number change with overall survival (OS) and disease-free survival (DFS) times. Two mtDNA polymorphisms were genotyped using the TaqMan(®) SNP genotyping technique and the genotypes for the remaining four mtDNA polymorphisms were obtained by the Illumina(®) HumanOmni1-Quad genome wide SNP genotyping platform in 536 patients. The mtDNA copy number change (in tumor tissues with respect to non-tumor tissues) was estimated using the quantitative real time polymerase chain reaction for 274 patients. Associations of these mtDNA variations with OS and DFS were tested using the Cox regression method.
  
  
  RESULTS
  In both univariate and multivariable analyses, none of the six mtDNA polymorphisms were associated with OS or DFS. 39.6 and 60.4% of the patients had increased and decreased mtDNA copy number in their tumor tissues when compared to their non-tumor rectum or colon tissues, respectively. However, in contrast to previous findings, the change in the mtDNA copy number was associated with neither OS nor DFS in our patient cohort.
  
  
  CONCLUSIONS
  Our results suggest that the mitochondrial genetic markers investigated in this study are not associated with outcome in colorectal cancer.
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John's, NL, A1B 3V6, Canada. amhm38@med.mun.ca.
authors.forename: Asan Meera Sahib Haja
authors.initials: AM
authors.lastname: Mohideen
authors.affiliation: Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. edicks@mun.ca.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dicks
authors.affiliation: Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. pparfrey@mun.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Parfrey
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John's, NL, A1B 3V6, Canada. rcgreen@mun.ca.
authors.forename: Roger
authors.initials: R
authors.lastname: Green
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, HSC, Room H4333, St. John's, NL, A1B 3V6, Canada. savas@mun.ca.|Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. savas@mun.ca.
authors.forename: Sevtap
authors.initials: S
authors.lastname: Savas
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D004272:DNA, Mitochondrial