The study, by scientists at 13 research centers, found that mutations in a gene known as EphB2 occurred in 15 percent of African-American men with a strong family history of prostate cancer. The mutation was found in only 5 percent of African-American men with no family or personal history of the disease and in less than 2 percent of European-American men with no history of the disease.
Prostate cancer rates are extremely high in African-American men. They develop the disease 60 percent more often than do European Americans, and they are almost two and half times more likely to die of the disease.
Until now, no gene mutations have been identified that contribute to hereditary prostate cancer and prostate-cancer susceptibility specifically in African-American men.
The findings are published online in the Sept. 9, 2005, issue of the Journal of Medical Genetics.
"This is the first gene mutation to be associated with familial prostate cancer in African-American men," says first author Rick A. Kittles, associate professor of molecular virology, immunology and medical genetics and a researcher with the Human Cancer Genetics program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
"Next, we must learn more about how this mutation contributes to cancer, and we must screen for the mutation in a much larger group of African-American men with prostate cancer to verify its association with the disease."
Then, says Kittles, a specialist in prostate-cancer genetics in African Americans, "perhaps we can begin using this mutation to help estimate prostate-cancer risk in African-American men."
The findings are the first to come out of the African-American Hereditary Prostate Cancer (AAHPC) study network, a group of 112 African-American families nationally who have volunteered to help in research to identify genetic risk factors for prostate cancer. Families in the network have had four or more cases of prostate cancer in the family.
"This as an exciting extension to our original findings implicating EphB2 as a prostate-cancer tumor-suppressor gene," says principal investigator John D. Carpten, of the Translational Genomics Research Institute.
"These data now suggest that mutations in this gene might predispose African-American men to prostate cancer in a significant way."
Other evidence suggesting that EphB2 could be a prostate-cancer susceptibility gene include its location on chromosome 1. The exact function of the gene is unknown.
For this study, the researchers isolated the EphB2 gene from white blood cells taken from 72 African-American men in the AAHPC with hereditary prostate cancer and examined them for mutations.
After sequencing the gene from each volunteer, the investigators found that 11 of the 72 men (15.3 percent) had a mutation designated K1019X. The same mutation was found in only 5.2 percent in a control group of 329 healthy African-American men and in only 1.7 percent of 231 European-American control samples.
The findings indicate that the K1019X mutation is found mainly in African-American men, that it is particularly prevalent in African-American men with a family history of prostate cancer, and that it increases the risk of prostate cancer in these men almost three-fold.
"Given its high frequency in hereditary cases, we believe that this mutation is probably associated with hereditary prostate cancer in African-American men," Kittles says.
Funding from the National Institutes of Health (NIH) Center for Minority Health and Health Disparities, the National Cancer Institute, the Department of Defense, the U.S. Public Health Service and the Commonwealth of Pennsylvania supported this research.
The other centers participating in the study were the Fox Chase Cancer Center; Translational Genomics Research Institute; the National Genome Center at Howard University; The University of Texas MD Anderson Cancer Center; University of California Davis Cancer Center; Midtown Urology Surgical Center, Atlanta, Georgia; Columbia University Medical Center; the University of Illinois at Chicago; Medical College of Georgia School of Nursing; National Human Genome Research Institute; the NIH Center for Inherited Disease Research; and the Karmanos Cancer Institute.
Contact: Darrell E. Ward, Medical Center Communications, 614-293-3737, or Ward-15@medctr.osu.edu
Journal
Journal of Medical Genetics