Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast cancer and benign breast diseases

Abstract

The mitochondrial DNA (mtDNA) 4977-bp deletion ( mtDNA 4977 mutation) is one of the most frequently observed mtDNA mutations in human tissues, and may play a role in carcinogenesis. Only a few studies have evaluated mtDNA 4977 mutation in breast cancer tissue, and the findings have been inconsistent, which may be due to methodological differences. In this study, we developed a quantitative real-time PCR assay to assess the level of the mtDNA 4977 mutation in tumor tissue samples from 55 primary breast cancer patients and 21 patients with benign breast disease (BBD). The mtDNA 4977 mutation was detected in all of the samples with levels varying from 0.000149% to 7.0%. The mtDNA 4977 mutation levels were lower in tumor tissues than in adjacent normal tissues in both breast cancer and BBD subjects. The differences, however, were not statistically significant. No significant difference between breast cancer and BBD patients was found in the mtDNA 4977 mutation levels of tumor tissues and adjacent normal tissues. The mtDNA 4977 mutation levels were not significantly associated with clinicopathological characteristics (age, histology, tumor stage, and ER/PR status) in breast cancer or BBD patients. These results do not support the notion that the mitochondrial DNA 4977-bp deletion plays a major role in breast carcinogenesis.

The 4977bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more?

“…In case of human oocytes it has been confirmed that age exhibits the only significant correlation with the presence of the 4977 bp deletion, while other parameters like smoking or early follicular phase FSH did not reveal any correlation (Chan et al, 2005). In recent years, a number of carefully conducted studies reported, that the level of the 4977 bp deletion is not increased in different tumour tissues (Dani et al, 2004;Dai et al, 2006;Ye et al, 2007) and in conditions associated with chronic inflammation like ulcerative colitis (Fukushima and Fiocchi, 2004). Though our data display a great variability even in individuals of the same age group, the large pool of data may help to discriminate between physiological ageing and pathological conditions associated with accelerated ageing.…”

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

“…However, the pathogenesis of mtDNA decrease in cancers remains unclear. It was hypothesised that mitochondrial respiratory dysfunction and damage of mtDNA, such as mutation, deletion or depletion, in carcinogenesis may course the quantitative alterations (Ye et al 2008). Those alterations of mtDNA could correlate with increased risk (Mosquera-Miguel et al 2008;Bai et al 2007) and increased invasiveness of cancer (Simonnet et al 2002).…”

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

“…The common mtDNA 4,977-bp deletion has been shown to accumulate with age, primarily in postmitotic tissues (13) and cancers (20)(21)(22)(23)(24). The different accumulation rate could result from genetic factors (such as tissue type), energy demand, intracellular oxidative stress levels, environmental insults, or cancer progression.…”

“…In addition, it is increased by environmental insults, such as UV irradiation (15)(16)(17), cigarette smoking (18,19) and betel quid chewing (20). Moreover, the mtDNA 4,977-bp deletion is also frequently detected in various types of cancer tissues (20)(21)(22)(23)(24). Due to its good correlation with oxidative damage levels in somatic tissues, we hypothesized that the mtDNA deletion would be more frequently detected in breast tissues of the patients with NQO1 609 C/T or T/T genotype than those with C/C genotype.…”