Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.

Autor: Domínguez-de-la-Cruz E; Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico., Muñoz ML; Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico. Electronic address: lmunoz@cinvestav.mx., Pérez-Muñoz A; Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico., García-Hernández N; Unidad de Investigación Médica en Genética Humana, Centro Médico Nacional (CMN) Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico., Moctezuma-Meza C; Unidad Médica de Alta Especialidad, Hospital de Ginecología y Obstetricia No. 3 'Dr. Víctor Manuel Espinosa de los Reyes Sánchez, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico., Hinojosa-Cruz JC; Unidad Médica de Alta Especialidad, Hospital de Ginecología y Obstetricia No. 3 'Dr. Víctor Manuel Espinosa de los Reyes Sánchez, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Jazyk: angličtina
Zdroj: Gene [Gene] 2020 Nov 30; Vol. 761, pp. 145047. Date of Electronic Publication: 2020 Aug 09.
DOI: 10.1016/j.gene.2020.145047
Abstrakt: Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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