Do Alterations in Mitochondrial DNA Play a Role in Breast Carcinogenesis?

J Oncol. 2010;2010:604304. Epub 2010 Jun 6.

Do alterations in mitochondrial DNA play a role in breast carcinogenesis?
Rohan TE, Wong LJ, Wang T, Haines J, Kabat GC.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx,NY 10461, USA.

Abstract
A considerable body of evidence supports a role for oxidative stress in breast carcinogenesis. Due to their role in producing energy via oxidative phosphorylation, the mitochondria are a major source of production of reactive oxygen species, which may damage DNA. The mitochondrial genome may be particularly susceptible to oxidative damage leading to mitochondrial dysfunction. Genetic variants in mtDNA and nuclear DNA may also contribute to mitochondrial dysfunction. In this review, we address the role of alterations in mtDNA in the etiology of breast cancer. Several studies have shown a relatively high frequency of mtDNA mutations in breast tumor tissue in comparison with mutations in normal breast tissue. To date, several studies have examined the association of genetic variants in mtDNA and breast cancer risk. The G10398A mtDNA polymorphism has received the most attention and has been shown to be associated with increased risk in some studies. Other variants have generally been examined in only one or two studies. Genome-wide association studies may help identify new mtDNA variants which modify breast cancer risk. In addition to assessing the main effects of specific variants, gene-gene and gene-environment interactions are likely to explain a greater proportion of the variability in breast cancer risk.

PMID: 20628528 [PubMed - in process]PMCID: PMC2902128
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Do Alterations in Mitochondrial DNA Play a Role in Breast Carcinogenesis?