Answers in ancestry
Doctors do not yet have a good handle on how a man's genetic inheritance affects his chances of developing prostate cancer. Dana-Farber's Matthew Freedman, MD, aims to find out.
"Although humans are 99.9 percent identical at the genetic level, there remain millions of variants in the human genome [the gallery of all genes within human cells]. Our goal is to find the ones associated with prostate cancer," explains Freedman. Considering that the genome has some 3 billion base pairs, or building blocks, of DNA, the task might seem akin to probing half the earth's population for a handful of people. The job has become manageable by technological advances, decreasing costs, and sophisticated analytic software. Just a few years ago, however, it was economically impractical to search the entire genome, so Freedman and his colleagues took a methodological shortcut.
They used a method known as admixture mapping that speeds the search for disease-related genes in patients with recent mixed ancestry, where one ancestral group has a higher rate of the disease in question. The method's main benefit is that it allows investigators to scan the whole genome using a couple thousand genetic markers, rather than the hundreds of thousands needed to survey the genome in more homogenous populations.
Because African Americans have a 1.6-times higher incidence of prostate cancer than people of European descent, Freedman scanned patients' genomes for regions of chromosome that were especially abundant in DNA from African ancestors. Such regions "enriched" with African DNA associated with elevated prostate cancer risk. The technique enabled Freedman to focus on sections where prostate cancer-linked differences are most likely to lurk.
In a study published earlier this year, Freedman's team used admixture mapping to identify a short section of chromosome 8q24 linked to an increased susceptibility to prostate cancer. The study used tissue samples from 1,600 African-American men, most of whom had prostate cancer. "To our knowledge, this is the first time admixture mapping has been used to pinpoint a chromosomal region associated with increased cancer risk," says Freedman, noting that the method may prove useful for other types of cancer as well.
"The area we've identified contains nine genes," he continues. "The challenge now is to find which of this group is chiefly responsible for the heightened risk of prostate cancer. What does it mean if an individual carries this genetic risk factor? Does it place him at risk for early-onset cancer? For an aggressive form of the disease? Population-based genetic research will help answer those kinds of questions."
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