Reactive oxygen species (ROS), generated predominantly by the electron transport chain that takes place in the mitochondria, have been associated with a number of human diseases, including cancer[1]. It has also been observed that mitochondrial genetic variation is associated with oxidative stress markers, the inhibition of oxidative phosphorylation, the promotion of tumour development and the ability of cancer cells to metastasize[2].
Because of the increased exposure to high ROS levels produced during respiration, lack of protective histones, and limited capacity for DNA repair[3,4] human mtDNA carries a large number of mutations that have segregated during evolution. Some of these genetic variants are used to define mtDNA haplogroups, and a few of them slightly modify metabolic performance and energy production; thus not all haplogroups have identical metabolic capacities[1]. It has been hypothesized that the geographic distribution of mtDNA haplogroups is the result of the selection of metabolic properties driven mainly by adaptation to climate and nutrition[1].
Nine mtDNA haplogroups have been identified in Europeans (namely H, I, J, K, T, U, V, W, X) which show varying frequencies by population. Particular haplogroups have been associated with breast cancer risk but no strong evidence of an effect has been found yet, inconsistencies being attributed to population stratification, genotyping error and inadequate design or statistical analysis[5].