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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 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."

"These findings support the notion that variations in the genetic sequence of mitochondrial DNA are underappreciated factors in breast carcinogenesis," said Jeffrey Canter, M.D., M.P.H., of the Center for Human Genetics Research at Vanderbilt University, Nashville, Tenn.

The mitochondria, located outside the nucleus, are the cell's energy-producing factories. Unlike chromosomal DNA, the mitochondrial DNA is passed to offspring exclusively from the mother and carries important information necessary for the production of adenosine triphosphate, 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 the blueprint for an important component of an enzyme called NADH dehydrogenase. In its changed state, however, an adenine is substituted for a guanine in the DNA structure, resulting in the enzyme containing the amino acid threonine instead of an alanine.

The clinical implication of this seemingly trivial alteration is profound. Among the greater population of humans, carriers of 10398A appear to be at higher risk for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and other neurological disorders.

Canter and colleagues determined that the errant allele is associated with a significantly higher risk for breast cancer among African-American women who carry 10398A, but has no apparent implications for breast cancer in white women. A much greater proportion of the white female population, 80 percent, already carries the 10398A version of the NADH dehydrogenase gene than the five percent of black American women with the allele.

In a pilot study conducted by Canter and his colleagues at Vanderbilt University, the mitochondrial allele appeared to be associated with a three-fold increase in the risk of African-American women developing invasive breast cancer. The evidence in the initial Vanderbilt study compelled Canter and his colleagues to investigate the ramifications of 10398A among a much larger group of women.

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

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 women participating in the Carolina Breast Cancer Study made this discovery possible. Their willingness to take part in this outstanding population-based study and contribute DNA for genetic analysis is a remarkable legacy," stated Canter.

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

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

###

Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: "Cancer Research"; "Clinical Cancer Research"; "Molecular Cancer Therapeutics"; "Molecular Cancer Research"; and "Cancer Epidemiology, Biomarkers & Prevention." AACR's Annual Meetings attract nearly 16,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.


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 April 18, 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 April 18, 2014).

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