Risky Legacy: African DNA linked to prostate cancer

The high rate of prostate cancer among African American men may result in large part from a newly identified stretch of DNA passed down from their African ancestors.

A black man’s odds of developing prostate cancer by age 55 are more than twice those of a white man. The racial discrepancy is less pronounced when the disease appears later. Researchers have suspected for years that genetic factors account for part of the racial difference in risk.

Most African Americans have both African and European forebears, so their chromosomes are mosaics of genes from the two continents. Previously identified genetic markers indicate that in U.S. blacks, an average of about 80 percent of the DNA is African in origin.

Geneticists have long hypothesized that they could identify disease-causing chunks of DNA by sifting through the genomes of ethnically mixed populations and noting where people with a disease tend to have genes from the same ancestral source, says David Reich of Harvard Medical School in Boston. Recent technical advances have made this approach feasible.

Reich and his colleagues analyzed the genomes of nearly 1,600 African Americans who had developed prostate cancer. In those men, a portion of chromosome 8 containing nine known genes was more frequently of African origin than were other portions of the DNA.

When the team tested nearly 900 cancer-free African American men, African ancestry of DNA turned up no more frequently in the implicated portion of chromosome 8 than elsewhere in their genomes.

Those findings suggest that having African rather than European DNA at the chromosome-8 location places a man at high risk of prostate cancer, the researchers report in an upcoming Proceedings of the National Academy of Sciences.

The team found the most dramatic link between men’s developing cancer at a young age and having the African chunk of DNA. “The risk factor we’ve identified is clearly more important for younger men than for older men,” Reich says.

That finding is the study’s most important new observation, says geneticist B. Jill Williams of Louisiana State University Health Sciences Center in Shreveport.

Its other findings merely confirm data reported in the June Nature Genetics, contends Kári Stefánsson of deCODE Genetics in Reykjavik, Iceland. In that study, he and his colleagues linked an elevated risk of prostate cancer to a gene variant in the chromosome-8 segment examined by Reich’s team. That variant is carried by nearly one-third of African Americans but appears at lower frequencies in Europeans and white Americans, Stefánsson says.

However, the variant identified by Stefánsson’s group explains only a fraction of the newly reported association between prostate cancer and African ancestry in the critical stretch of chromosome 8. “There must be important and unidentified risk factors for prostate cancer in this section of genetic material,” Reich concludes.

“It’s also possible and, I think, more likely that there are other variants of the same gene,” counters Stefánsson.