Results from two genome-wide association studies have identified a genetic variant of the DAB2IP gene that is associated with the risk of aggressive prostate cancer. Research teams from the Translational Genomics Research Institute (TGen) in Phoenix, Wake Forest University School of Medicine in Winston-Salem, NC, the Karolinska Institute in Stockholm, Sweden, and Johns Hopkins Medical Institutions in Baltimore made the discovery jointly.
Researchers suspect that the DAB2IP gene is involved in tumor suppression, suggesting that this protective mechanism goes awry in men with the variant form. The finding, published in the Dec. 11, 2007, online edition of the Journal of the National Cancer Institute, might one day help physicians tailor treatment based on a patient’s genetic makeup.
"Because there is no way to tell whether a person has or will have the aggressive version versus the mild version of prostate cancer, both forms are treated the same-with radiotherapy or surgery to remove the prostate gland,” said senior author John Carpten, PhD, of TGen. “The identification of this genetic variant could lead to better risk assessment for aggressive disease, providing doctors with more information on how to best treat men who may be diagnosed with prostate cancer.”
Analysis of 3,159 samples led the researchers to conclude that men possessing the DAB2IP variant appear to carry a nearly 36% increased risk of advanced prostate cancer. The researchers screened DNA samples from 500 men with advanced prostate cancer and 500 healthy men of the same age in Sweden. This DNA screening examined the entire genome for more than 550,000 single nucleotide polymorphisms (SNPs), which are locations on chromosomes where a single unit of DNA may vary from one person to the next. The team then focused on 60,000 SNPs that have also been evaluated by a similar study conducted by the National Cancer Institute. Evaluation of these 60,000 SNPs identified seven SNPs that appeared to be linked to disease aggressiveness.
Additionally, researchers screened another 1,242 men with advanced disease and 917 healthy men who were part of a research project at Johns Hopkins. This group included both African and European Americans. Through these multiple screenings, the researchers found that the variant form of DAB2IP is associated with an increased risk of aggressive disease.