Association between mitochondrial DNA 4,977 bp deletion and NAD(P)H:quinone oxidoreductase 1 C609T polymorphism in human breast tissues.
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 > or =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.
Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan 112, ROC.
Ling-Ming
LM
Tseng
Pen-Hui
PH
Yin
Yi-Fang
YF
Tsai
Chin-Wen
CW
Chi
Chew-Wun
CW
Wu
Liang-Ming
LM
Lee
Hsin-Chen
HC
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D004272:DNA, Mitochondrial; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human