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Do alterations in mitochondrial DNA play a role in breast carcinogenesis?

Rohan TE, Wong LJ, Wang T, Haines J, Kabat GC - J Oncol (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

No MeSH data available.


Related in: MedlinePlus

See work by Taanman in [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system (DiMauro and Schon, 2003) [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].
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fig2: See work by Taanman in [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system (DiMauro and Schon, 2003) [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].

Mentions: Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is transmitted through the female germline [77]. MtDNA is located in the mitochondrial matrix and is present in multiple copies per mitochondrion [38, 77]. The human mitochondrial genome is a closed, double-stranded DNA molecule of 16,569 bp, which contains 37 genes. Most of the genes are located on the heavy (H) strand, which encodes for two ribosomal RNAs, 14 transfer RNAs (tRNAs), and 12 polypeptides (Figure 2) [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement-loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].


Do alterations in mitochondrial DNA play a role in breast carcinogenesis?

Rohan TE, Wong LJ, Wang T, Haines J, Kabat GC - J Oncol (2010)

See work by Taanman in [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system (DiMauro and Schon, 2003) [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902128&req=5

fig2: See work by Taanman in [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system (DiMauro and Schon, 2003) [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].
Mentions: Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is transmitted through the female germline [77]. MtDNA is located in the mitochondrial matrix and is present in multiple copies per mitochondrion [38, 77]. The human mitochondrial genome is a closed, double-stranded DNA molecule of 16,569 bp, which contains 37 genes. Most of the genes are located on the heavy (H) strand, which encodes for two ribosomal RNAs, 14 transfer RNAs (tRNAs), and 12 polypeptides (Figure 2) [38]. The light (L) strand encodes for eight tRNAs and a single polypeptide. The 13 protein products are subunits of the enzyme complexes of the respiratory chain/oxidative phosphorylation system [37]. Mammalian mtDNA does not have introns, and has only a few intergenic sequences. The displacement-loop (D-loop) region is a short, three-stranded structure in which a short nucleic acid strand, complementary to the L-strand, displaces the H-strand. The D-loop is the major control site for mtDNA expression, containing the leading-strand origin of replication and the major promoters for transcription [38].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

No MeSH data available.


Related in: MedlinePlus