title: Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.
abstract: 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.
authors.affiliation: IMBICE, Instituto Multidisciplinario de Biología Celular, La Plata, Argentina.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Pavicic
authors.forename: Martin
authors.initials: M
authors.lastname: Laguens
authors.forename: Silvina M
authors.initials: SM
authors.lastname: Richard
mesh_terms: 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
chemical_list: D001191:Arylamine N-Acetyltransferase; D004272:DNA, Mitochondrial; D005982:Glutathione Transferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1