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.
Pavicic
Walter H
WH
IMBICE, Instituto Multidisciplinario de Biología Celular, La Plata, Argentina.
Laguens
Martin
M
Richard
Silvina M
SM
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial / Q000235:genetics*; D042822:Genomic Instability; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics
D001191:Arylamine N-Acetyltransferase; D004272:DNA, Mitochondrial; D005982:Glutathione Transferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1