Correlation analysis between mtDNA 4977-bp deletion and ageing.

Mitochondrial DNA 4977-bp deletion (common deletion) has been associated with ageing human tissues and a few studies have demonstrated their presence in breast cancer patients too; however, no previous publication evaluated both topics in the same samples group. First, when analyzing 95 breast cancer patients, we found a higher percentage of cases carrying the deletion in non-tumoral tissue 73.68% (70/95) than in the tumoral counterparts 45.26% (43/95), showing that the 4977-bp deletion is a phenomenon which commonly appear first in the non-tumoral breast tissue rather than tumoral tissue. Secondly, we analyzed and compared the ageing related distribution of the common deletion rates, in a control group of 199 samples (ages ranging from 10 to 80 years), with those found in cancer patients. Significant correlation was observed in control cases, between individual age ranges and rates of deletion (chi2: 23.21 and p<0.01). In contrast, non-tumoral breast tissue did not show a pattern of correlation, chi2: 0.042 and p: 0.837. However, interestingly, we found that the risk of having deleted mtDNAs was higher for non-tumoral breast samples than for the control group samples, OR: 2.32 [1.22-4.42, 95% CI]; this could be reflecting that other mechanisms are involved in mitochondrial genome deletion increased rate detected in breast cancer cases, than the normal ageing process.

Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.

The aim of this study was to determine the existence of association between the genetic polymorphisms of metabolizing genes GSTM-1, GSTT-1, and NAT-2, and the presence of mitochondrial genome instability (mtGI) in breast cancer cases. Ninety-four pairs of tumoral/nontumoral breast cancer samples were analyzed. Our samples showed 40.42% of mtGI by analysis of two D-loop region markers, a (CA)n mtMS starting at the 514-bp position, and four informative MnlI sites between the 16,108-16,420-bp. GSTM-1 null genotype has shown a significant association with mtGI presence (chi(2) = 7.62; P = 0.006) in breast cancer cases; moreover, these genotypes also are related to an increased risk for mtDNA damage (odds ratio [OR] = 3.71 [1.41-9.88]; 95% Cornfield confidence interval [CI]). These results suggest that the absence of GSTM-1 enzymatic activity favors chemical actions in damaging the mtDNA. Analysis of GSTT-1 and NAT-2 polymorphisms showed no association with mtGI (chi(2) = 0.03; P = 0.87 and chi(2) = 2.76; P = 0.09, respectively). The analysis of invasive breast cancer cases showed mtGI in 74.36% of ILC cases (29 of 39 samples), and in only 18.75% (9 out of 48) IDC cases; this result suggests a possible relation between mtDNA mutations and variations in molecular pathways of tumor development.