Chromosome 8q24 Linked to Elevated Prostate Cancer Risk in African Americans

Abstract

Researchers from Dana-Farber Cancer Institute and Harvard Medical School have found a region of the human genome that accounts for the higher risk of prostate cancer in black Americans.Matthew Freedman, MD, a Dana-Farber researcher and lead author of a paper in the August 21, 2006 online version of the Proceedings of the National Academy of Sciences, said the genetic factor lies in a group of genes located on a region of the eighth human chromosome. Depending on their ancestry, black men may have inherited the DNA segment (actually, there are two copies of it) from lineage going directly back to Africa, or from European ancestors, or from both. The data indicate that those who have inherited this chromosomal region from African rather than European ancestors have a higherprostate cancer risk."This is one of the first times that a genetic risk factor has been identified in the general population that contributes to prostate cancer risk, and which may give us an insight into the underlying biology of the disease," said Freedman, who is also affiliated with Harvard Medical School and the Broad Institute of MIT and Harvard.Freedman and his collaborators are carrying out further work to pinpoint which of nine genes within the African-derived DNA segment, designated 8q24 on a "map" of the chromosomes, actually causes the cancer susceptibility. "This could give us an insight into molecular pathways that trigger the development of prostate cancer, and what therapies you might use in treating it," Freedman said. Last May, an Icelandic gene-hunting company first announced the discovery of a genetic risk factor that explained the prostate cancer disparity. The genetic variant identified by the company, deCODE Genetics, is physically located in the same region described by the new report, but is not itself the cause of the heightened cancer susceptibility, say the Dana-Farber and Harvard scientists.David Reich, PhD, senior author of the PNAS report, said, "This paper is important because it confirms what deCODE found: our two groups have independently converged on the same region. I'm absolutely convinced that this explanation for the difference in prostate cancer susceptibility is real."The results of both studies show that the genetic risk factor operates more strongly at younger ages, and becomes less marked at older ages. Black men who inherited the DNA segment from African ancestors and are younger than 55 have a 2.3-fold higher risk of developing prostate cancer. However, by age 72, the difference in risk declines to 1.4 times higher.Reich, Freedman and their co-authors used a powerful technique called "admixture mapping" to focus the search through 23 pairs of chromosomes, carrying a total 3.5 billion letters of genetic code -- the genome -- to find disease-susceptibility genes. In a multi-ethnic sample of patients, according to the "admixture" concept, it islikely that near a disease-causing gene there will be a marked abundance of DNA from the population that has the greater risk of developing the disease.In this case, the technique enabled scientists to test African American prostate cancer patients, as well as groups without the disease, and noticed a region on Chromosome No. 8 with an enrichment of DNA inherited from African, as opposed to European, lineages. That was a sign that the genetic factor for increased prostate cancer susceptibility was in the neighborhood.The result was the identification of a region comprising 3.8 million bases, or letters of the genetic code, associated with elevated risk of prostate cancer. It is within those 3.8 million letters, believed to contain nine genes as well as a large amount of DNA extraneous to the genes, that the causative genetic difference is expected to be found.In addition to Freedman and Reich, authors include Brian E. Henderson, MD, of the University of Southern California, and David Altshuler, MD, PhD, of the Broad Institute and Harvard Medical School.The research was supported by grants from the National Institutes of Health.Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center, designated a comprehensive cancer center by the National Cancer Institute.For more information, contact: Bill Schaller or Richard Saltus; Tel.: 617.632.4090