Mitochondrial Control Region Variants Related to Breast Cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Our purpose was to explore differences in mitochondrial sequences of cases with breast cancer compared with control samples from different origins. We identified 124 mtDNA sequences associated with breast cancer cases, of which 86 were complete and 38 were partial sequences. Of these 86 complete sequences, 52 belonged to patients with a confirmed diagnosis of breast cancer, and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From the mtDNA analysis, two polymorphisms with significant statistical differences were found: m.310del (rs869289246) in 34.6% (27/78) of breast cancer cases and 61.7% (21/34) in the controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) in the controls. In addition, the variant m.16519T>C (rs3937033) was found in 59% of the control sequences and 52% of the breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to the haplogroup H of Indo-European and Euro-Asiatic origins; however, they were found in all non-European breast cancers.

Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial.

In heart failure patients the consumption of (-)-epicatechin ((-)-Epi)-rich cocoa can restore skeletal muscle (SkM) mitochondrial structure and decrease biomarkers of oxidative stress. However, nothing is known about its effects on exercise capacity and underlying mechanisms in normal, sedentary subjects. Twenty normal, sedentary subjects (∼50 years old) were randomized to placebo or dark chocolate (DC) groups and consumed 20 g of the products for 3 months. Subjects underwent before and after treatment, bicycle ergometry to assess VO2 max and work, SkM biopsy to assess changes in mitochondrial density, function and oxidative stress and blood sampling to assess metabolic endpoints. Seventeen subjects completed the trial. In the DC group (n = 9), VO2 max increased (17% increase, p = 0.056) as well as maximum work (watts) achieved (p = 0.026) with no changes with placebo (n = 8). The DC group evidenced increases in HDL levels (p = 0.005) and decreased triglycerides (p = 0.07). With DC, SkM evidenced significant increases in protein levels for LKB1, AMPK and PGC1α and in their active forms (phosphorylated AMPK and LKB1) as well as in citrate synthase activity while no changes were observed in mitochondrial density. With DC, significant increases in SkM reduced glutathione levels and decreases in protein carbonylation were observed. Improvements in maximum work achieved and VO2 max may be due to DC activation of upstream control systems and enhancement of SkM mitochondria efficiency. Larger clinical studies are warranted to confirm these observations.