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Breast Cancer Risk Increased For African-Americans With Mitochondrial DNA Variant

Date:
September 1, 2005
Source:
American Association for Cancer Research
Summary:
African-American women who carry the 10398A mitochondrial DNA allele are 60 percent more likely to develop invasive breast cancer than African-American females without that genetic marker, according to research published in the September 1 issue of "Cancer Research."

PHILADELPHIA--African-American women who carry the 10398A mitochondrialDNA allele are 60 percent more likely to develop invasive breast cancerthan African-American females without that genetic marker, according toresearch published in the September 1 issue of "Cancer Research."

"These findings support the notion that variations in the geneticsequence of mitochondrial DNA are underappreciated factors in breastcarcinogenesis," said Jeffrey Canter, M.D., M.P.H., of the Center forHuman Genetics Research at Vanderbilt University, Nashville, Tenn.

The mitochondria, located outside the nucleus, are the cell'senergy-producing factories. Unlike chromosomal DNA, the mitochondrialDNA is passed to offspring exclusively from the mother and carriesimportant information necessary for the production of adenosinetriphosphate, ATP, the energy source for cellular function.

In this study, the researchers focused on a specific variation(G10398A) in a mitochondrial gene called ND3, which serves as theblueprint for an important component of an enzyme called NADHdehydrogenase. In its changed state, however, an adenine is substitutedfor a guanine in the DNA structure, resulting in the enzyme containingthe amino acid threonine instead of an alanine.

The clinical implication of this seemingly trivial alterationis profound. Among the greater population of humans, carriers of 10398Aappear to be at higher risk for Parkinson's disease, Alzheimer'sdisease, amyotrophic lateral sclerosis (Lou Gehrig's disease), andother neurological disorders.

Canter and colleagues determined that the errant allele isassociated with a significantly higher risk for breast cancer amongAfrican-American women who carry 10398A, but has no apparentimplications for breast cancer in white women. A much greaterproportion of the white female population, 80 percent, already carriesthe 10398A version of the NADH dehydrogenase gene than the five percentof black American women with the allele.

In a pilot study conducted by Canter and his colleagues atVanderbilt University, the mitochondrial allele appeared to beassociated with a three-fold increase in the risk of African-Americanwomen developing invasive breast cancer. The evidence in the initialVanderbilt study compelled Canter and his colleagues to investigate theramifications of 10398A among a much larger group of women.

"Through our collaboration with Dr. Robert Millikan, at theUniversity of North Carolina, we validated the Vanderbilt finding witha larger number of women who participated in the Carolina Breast CancerStudy," Canter said. "We looked at 1259 women including 654 breastcancer patients. African-American women with the 10398A allele in thislarger study had a significantly increased risk for invasive breastcancer."

The change in cellular function due to the single amino acid substitution encoded by 10398A remains to be defined, Canter said.

"The hundreds and hundreds of African-American womenparticipating in the Carolina Breast Cancer Study made this discoverypossible. Their willingness to take part in this outstandingpopulation-based study and contribute DNA for genetic analysis is aremarkable legacy," stated Canter.

"We suspect that the mitochondrial 10398A allele impairs thefunction of the mitochondrial electron chain, resulting in increasedoxidative stress and breast cancer susceptibility," Canter said.

Canter's colleagues included Vanderbilt University researchersAsha Kallianpur, M.D., M.P.H, and Fritz Parl, M.D., Ph.D.; and RobertMillikan, D.V.M., Ph.D., University of North Carolina, at Chapel Hill.

###

Founded in 1907, the American Association for Cancer Research is aprofessional society of more than 24,000 laboratory, translational, andclinical scientists engaged in all areas of cancer research in theUnited States and in more than 60 other countries. AACR's mission is toaccelerate the prevention and cure of cancer through research,education, communication, and advocacy. Its principal activitiesinclude the publication of five major peer-reviewed scientificjournals: "Cancer Research"; "Clinical Cancer Research"; "MolecularCancer Therapeutics"; "Molecular Cancer Research"; and "CancerEpidemiology, Biomarkers & Prevention." AACR's Annual Meetingsattract nearly 16,000 participants who share new and significantdiscoveries in the cancer field. Specialty meetings, held throughoutthe year, focus on the latest developments in all areas of cancerresearch.


Story Source:

The above story is based on materials provided by American Association for Cancer Research. Note: Materials may be edited for content and length.


Cite This Page:

American Association for Cancer Research. "Breast Cancer Risk Increased For African-Americans With Mitochondrial DNA Variant." ScienceDaily. ScienceDaily, 1 September 2005. <www.sciencedaily.com/releases/2005/09/050901072326.htm>.
American Association for Cancer Research. (2005, September 1). Breast Cancer Risk Increased For African-Americans With Mitochondrial DNA Variant. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2005/09/050901072326.htm
American Association for Cancer Research. "Breast Cancer Risk Increased For African-Americans With Mitochondrial DNA Variant." ScienceDaily. www.sciencedaily.com/releases/2005/09/050901072326.htm (accessed August 28, 2014).

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