Mitochondrial Haplogroups, Control Region Polymorphisms and Malignant Melanoma: A Study in Middle European Caucasians

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.

Mitochondria and Cancer: Past, Present, and Future

“…It is important to use blood as control tissue measurements because it is necessary to subtract out mtDNA variation that arises from accumulation of damage over the lifespan, for example, due to aging. Direct analysis of haplogroups associated with cancer does not establish a correlation with variation of mtgenomes metastasis [60]. Comparison of control tissue to tumor tissue must be conducted with such samples collected from the same individual.…”

The Stance of Antioxidants in Brain Tumors

“…Cancer specific mitochondrial DNA mutations have been identified. Recent studies, associating the alterations in mitochondrial DNA and cancer risk, suggest mitochondrial DNA changes during cancer development are more complicated than estimated (Ebner, et al, 2011;Lam, et al 2012). …”

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer

“…These regions are associated with mitochondrial genome instability [113,114]. Multiple other hotspots have been identified in the D-loop region including the T16189C polymorphism in endometrial cancer [115], rectal cancer [116], melanoma [94], and prostate cancer [117,118]. Interestingly, this SNP has been associated with metabolic disease and type II diabetes [119,120], further supporting a linkage between mitochondrial polymorphisms, metabolism and neoplastic development.…”