Major Genetic Risk Factor Found For Prostate Cancer With The Highest Impact In Younger African Americans

"This paper identifies a genetic risk factor that about doubles the likelihood of prostate cancer in younger African American men," says principal investigator David Reich, PhD, Harvard Medical School assistant professor of genetics with the HMS Department of Genetics and the Broad Institute. "This finding may explain why younger African Americans have an increased risk for prostate cancer than do other populations--and may also explain why this increased risk in African Americans attenuates with older age."

"This is one of the first genetic risk factors found that is responsible for an appreciable fraction of sporadic prostate cancer cases, particularly for the African American population," says lead author Matthew Freedman, Harvard Medical School instructor of medicine at the Dana-Farber Cancer Institute and the Broad Institute "Interestingly, we found that this region also confers risk for prostate cancer for diverse ethnic groups. The actual gene, however, remains to be identified."

The researchers used their newly developed method of "admixture mapping" to screen through the genome in African Americans (who have both African and European ancestry), searching for the segments where individuals with disease have more of one ancestry than the average. The key epidemiological fact is that prostate cancer occurs approximately 1.6-fold times more often in African Americans than in other populations. This prompted the hypothesis that there is a genetic risk factor for prostate cancer that occurs at higher frequency in African than in other populations, and that can be found by searching for a region where the proportion of African ancestry is higher than the genome average.

Reich, Freedman and their colleagues studied 1,597 African Americans with prostate cancer. They found a section of the genome in the patients that had much more than the average proportion of African ancestry, rising from 78 percent to about 85 percent. The risk factor is localized to a tiny fraction (about a thousandth) of the genome, a section on chromosome 8 containing just 9 genes.

A particularly exciting aspect of this work is that in May a separate research team also identified a genetic variant occurring within the same region, which increases risk for prostate cancer. The study by Reich and colleagues makes two additional advances. One important result is that the genetic risk factor is more important for individuals with younger age. Second, they show that the specific genetic variant reported in the earlier paper can explain only at most a small fraction of the increased risk to African Americans. Thus, major unidentified risk factors remain to be found.