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Inherited variations in mitochondrial DNA linked to renal and prostate cancer


More than 20 million men in the United States with a particular signature set of inherited characteristics and mutations in mitochondrial DNA (mtDNA) are at significantly increased risk for developing renal and prostate cancers, according to research at Emory University. The findings will be presented at the 96th Annual Meeting of the American Association for Cancer Research by John A. Petros, MD, associate professor of urology at Emory University School of Medicine, its Winship Cancer Institute, and the Atlanta VA Medical Center.

Mitochondrial DNA, which contains a small number of genes inherited mainly from the mother, is found in the hundreds of mitochondria located in the cytoplasm outside of each cell’s nucleus. The mitochondria often are called the "powerhouse" of the cell because they produce about 90 percent of the body’s energy.

In a study comparing mtDNA of men from the general population to mtDNA of men with renal and prostate cancer, Dr. Petros found that only 9.6 percent of the general population of Caucasian Americans had mtDNA in haplogroup U, while 16.7 percent of prostate cancer patients and 20.7 percent of renal cancer patients exhibited the haplogroup U signature. A haplotype is a combination of variations in a gene.

In addition to the variations in haplogroup U, Dr. Petros also found that 12 percent of prostate cancer patients had several missense mutations in a mitochondrial gene called cytochrome C oxidase subunit I (COI) gene compared to less than 2 percent of patients with negative biopsies for prostate cancer. Missense mutations in genes lead to amino acid substitutions in the protein encoded by the gene.

"This is convincing evidence that mitochondrial variations and mutations play an important role in prostate and renal cancers," Dr. Petros said. "This is the first evidence that individuals who inherit these mutations are at increased risk of developing prostate cancer later in life. Mitochondrial genotyping has the potential of identifying this large number of at-risk individuals so that screening can be initiated for early detection and prevention."

Holly Korschun | EurekAlert!
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