Two tiny genetic variations may provide the best clues yet for finding more precise ways to estimate prostate cancer risk and improve screening and early detection for men of African descent, report researchers from the University of Chicago and the Translational Genomics Research Institute, Phoenix, AZ, in the December 2007 issue of Genome Research, published early online.
The researchers set out to determine whether results from four previous studies that linked genetic variations on one region of chromosome 8 to increased prostate cancer risk among Caucasians were also valid for men of African heritage. In the process, however, they found an additional genetic variation among African American men that was an even stronger marker for cancer risk for these men. That variation is located within a gene that plays a role in DNA repair. A malfunction in DNA repair could contribute to cancer development.
"This finding emphasizes the importance of ancestry in studying genetics," said study author Rick Kittles, associate professor of medicine at the University of Chicago Medical Center. "Previous studies led us to one specific region of chromosome 8," he said. "Then this approach -- which took advantage of genetic differences among African American men, who are at very high risk for this type of cancer -- led us to a different locus within that region and directly to a gene of interest.
Prostate cancer is the most common male malignancy and the second leading cause of cancer death in men. According to the American Cancer Society, it will affect nearly 220,000 men in the United States in 2007 and claim the lives of more than 27,000. It disproportionately affects African Americans who "exhibit the highest rate worldwide," Kittles said.
In this study, research groups lead by Kittles and by John Carpten of the Translational Genomics Research Institute analyzed the region of chromosome 8 highlighted by the earlier studies done on Caucasian men. But this time they searched for tiny genetic differences between 490 African American men who had been diagnosed with prostate cancer at Howard University Hospital in Washington, DC, and 567 African American men without cancer.
The researchers were able to replicate the linkage between one of the markers detected by previous studies and increased risk. More important, they found a new genetic marker, known as rs7008482, that was even more strongly associated with prostate cancer in African Americans. This marker was located within a gene that is involved in DNA replication, recombination and repair.
Altering this gene could confer an "inherited predisposition to genetic instability," Kittles said. "This could lead to increased cancer risk. By studying this region, we may be able to develop molecular targets for improved screening, early detection, and possibly treatment.
Multiple studies, the authors conclude, strongly support the existence of several independent genetic variants that could increase prostate cancer risk within this small region of chromosome 8. They have already begun to look closer at this region and to study the function of nearby genes.
The study also reinforces the need to keep ancestry in mind when looking at disease-gene genetics. Since African Americans vary significantly in genetic ancestral proportions and the prevalence of prostate cancer is almost two-fold higher among African Americans compared to European Americans," Kittles said, "the use of ancestry-informative markers for association with prostate cancer is quite powerful."
|Contact: John Easton|
University of Chicago Medical Center