Abstract
BackgroundBecause 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.Methodology and Principal FindingsUsing 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 and SignificanceOur results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated.
Highlights
Malignant melanoma is one of the most aggressive skin cancers arising from the pigment-producing cells called melanocytes
Our results suggest that mitochondrial DNA (mtDNA) variations could be involved in melanoma etiology and pathogenesis, the functional consequence of control region (CR) polymorphisms remains to be elucidated
The nine major European mtDNA haplogroups and CR polymorphisms were analyzed in whole blood samples of 351 patients with malignant melanoma and compared to 1598 control subjects [28]
Summary
Malignant melanoma is one of the most aggressive skin cancers arising from the pigment-producing cells called melanocytes. It has long been postulated that variation of mitochondrial functions may contribute to the development and progression of cancer [3] Mitochondria possess their own DNA (mtDNA), a circular double-stranded molecule consisting of 16,569 base pairs coding for 37 genes: 13 protein subunits of the electron transport chain, 22 tRNAs and 2 rRNAs. In addition, mtDNA contains a noncoding control region (CR), called the D-loop, with regulatory sequences controlling mtDNA replication and transcription [4]. It has been hypothesized that mtDNA mutations or inherited polymorphisms may alter the encoded protein subunits of the respiratory chain complexes. 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.
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