Association between mitochondrial DNA 4,977 bp deletion and NAD(P)H:quinone oxidoreductase 1 C609T polymorphism in human breast tissues

Abstract

Abstract. The NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme is implicated in protection against oxidative stress and carcinogenesis. NQO1 C609T genetic polymorphism was reported to be associated with an increased risk for cancers, including breast cancer. However, there is still lack of evidence whether higher oxidative stress occurs in breast tissues of patients with NQO1 609 C/T and/or T/T genotypes. Mitochondrial DNA (MtDNA) 4,977-bp deletion, the most common mutation of mtDNA, was frequently detected in post-mitotic tissues of aged subjects and associated with oxidative damage. In this study, we detected the mtDNA 4,977-bp deletion in 60 breast cancers and corresponding non-cancerous breast tissues. The incidence of the common 4,977-bp deletion in non-cancerous breast tissues (48.3%) was higher than that in breast cancer (5.0%). Moreover, 63.4% of the breast cancer patients with NQO1 C/T or T/T genotypes had the deletion in their non-cancerous breast tissues. The mtDNA deletion was more frequently detected in breast tissue of NQO1 C/T carriers (65.2%) and T/T carriers (61.1%) as compared with the NQO1 C/C carriers (15.8%, P=0.003). Similar results were observed in the <50 years old (y/o) group (P=0.06) and the ≥50 y/o group (P=0.005). Our findings suggest that mtDNA 4,977-bp deletion associated with NQO1 deficiency is involved in carcinogenesis and progression of breast cancer.

Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor

“…Various carcinoma cells exhibit large-scale mtDNA deletion, such as 4977 bp, which inhibit the reduction of 5 tRNA genes and 7 protein-encoding genes. NADPH quinone oxidoreductase 1 (NQO1) deficiency enhances the ROS production in oral and breast cancer due to mtDNA 4977 gene deletion [ 57 – 60 ]. The mtDNA mutations affect the complex I of the electron transport chain in metastatic cancers.…”

A influência dos polimorfismos CYP1A1 A4889G, CYP1A1 T6235C, NQO1 C609T e GSTP1 Ile105Val e da deleção homozigótica de GSTM1 e GSTT1 no risco e prognóstico dos pacientes com linfoma não-Hodgkin difuso de grandes células B

“…A enzima quinona óxido-redutase (NOQ1) é membro da família NAD(P)Hdehidrogenase e é amplamente expressa na fase II de detoxificação. Envolvida no metabolismo das quinonas, a enzima NAD(P)H: quinona oxidorredutase 1 (NQO1) é uma redutase obrigatória de dois elétrons que participa, predominantmente, da proteção contra efeitos tóxicos de quimioterápicos e na defesa contra ROS (Nioi e Hayes, 2004;Tseng LM et al, 2009).…”