title: Mitochondrial haplogroups, control region polymorphisms and malignant melanoma: a study in middle European Caucasians.
abstract: BACKGROUND
  Because mitochondria play an essential role in energy metabolism, generation of reactive oxygen species (ROS), and apoptosis, sequence variation in the mitochondrial genome has been postulated to be a contributing factor to the etiology of multifactorial age-related diseases, including cancer. The aim of the present study was to compare the frequencies of mitochondrial DNA (mtDNA) haplogroups as well as control region (CR) polymorphisms of patients with malignant melanoma (n = 351) versus those of healthy controls (n = 1598) in Middle Europe.
  
  
  RESULTS
  Using primer extension analysis and DNA sequencing, we identified all nine major European mitochondrial haplogroups and known CR polymorphisms. The frequencies of the major mitochondrial haplogroups did not differ significantly between patients and control subjects, whereas the frequencies of the one another linked CR polymorphisms A16183C, T16189C, C16192T, C16270T and T195C were significantly higher in patients with melanoma compared to the controls. Regarding clinical characteristics of the patient cohort, none of the nine major European haplogroups was associated with either Breslow thickness or distant metastasis. The CR polymorphisms A302CC-insertion and T310C-insertion were significantly associated with mean Breslow thickness, whereas the CR polymorphism T16519C was associated with metastasis.
  
  
  CONCLUSIONS
  Our results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated.
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ebner
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Edith E
authors.initials: EE
authors.lastname: Mueller
authors.forename: Waltraud
authors.initials: W
authors.lastname: Eder
authors.forename: Michaela
authors.initials: M
authors.lastname: Oeller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moser
authors.forename: Josef
authors.initials: J
authors.lastname: Koller
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D016022:Case-Control Studies; D021901:DNA, Intergenic / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D008969:Molecular Sequence Data; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D004272:DNA, Mitochondrial