Mitochondrial DNA variants linked to renal, prostate cancer

04/07/05

Anaheim, Calif. – It's often called the 'powerhouse" of the cell because this is where sugar is broken down to release energy required for cell function.

But mitochondria also contain a small amount of DNA that's used to manufacture 13 of the proteins needed for all these activities.

Now, scientists at Emory University have discovered that mitochondrial DNA contains signature sequencing that is associated with two times the risk for prostate and up to two-and-one-half times the risk for renal cancer.

"The inheritance of mitochondrial haplotype is important in cancer disposition," said John Petros, M.D., associate professor of urology at Emory University and The Atlanta VA Medical Center. A haplotype is a combination of variations in a gene.

Like an asterisk fixed alongside the human genome, mitochondrial DNA (mtDNA) contains additional inherited genetic information that is passed primarily from mother to offspring. Petros identified the U haplotype as a signal for increased risk of prostate and renal cancer.

"There is also inheritance of missense mutations in at least one mitochondrial gene that is important in prostate cancer," Petros said. Missense mutations in genes lead to amino acid substitutions in the protein encoded by the gene. Among mitochondrial genes, several missense mutations in the cytochrome C oxidase subunit I (COI) gene predisposed men to increased risk for prostate cancer as well, Petros' research indicated.

The U haplogroup is one of many segments of the human population that can be grouped according to the evolutionary quirks embedded with their mtDNA. The U haplotype developed among people migrating to northern and Eastern Europe thousands, or even tens of thousands of years ago. People who carry the U haplotype mtDNA belong to the U haplogroup.

Petros determined that among Caucasian Americans, the U haplogroup makes up 9.6 percent of the general population, but a disproportionate number of prostate and renal cancer patients are from the U haplogroup.

"We found that 16.7 percent of the prostate cancer patients and 20.7 percent of renal cancer patients are from the U haplogroup," Petros noted. "If you are a Caucasian American and are of haplogroup U, you have roughly twofold increased risk over other Caucasian American haplogroups.

For those who are U haplotype, Petros suggests extra vigilance in monitoring for prostate or renal cancer.

"If you are among the U group, there is a similarly increased risk comparable to having a positive family history or being African American," Petros said. "The most conventional, nationwide recommendations for screening suggest that high risk groups get screened earlier. That is the essence of what we suggest. We would begin screening with serum PSA and digital rectal exams say at 40 or 45 instead of 50. If you believe in screening for early detection and prevention, you would certainly want to be aggressive and early with it."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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