A gene scan that identifies an individual man’s DNA variants improves the predictive power of the test commonly used to gauge the risk of prostate cancer, a study from DeCode Genetics Inc. found.
The commonly used test measures prostate specific antigen, a protein in men’s blood that may rise when cancer is present. The exam also produces false-positive results. Reykjavik, Iceland-based DeCode analyzed the genomes of thousands of men and found those with certain gene variations had higher scores when tested for PSA. Adjusting the scores based on genetic profiles changed the risk for about 7 percent of the men, the study found.
The inaccuracy of the PSA test has fueled debate among doctors and medical societies about whether the test should be used to screen men with no evidence of cancer. Because the protein test isn’t always accurate, the screenings lead to needless treatment in some and misses cancer in others, said Otis Brawley, medical director of the American Cancer Society.
“The PSA test is problematic and it’s important to do anything we can to improve it,” said John Witte, associate director of the Institute for Human Genetics at the University of California, San Francisco. Tweaking PSA results using a gene profile “is a great step in the right direction but my sense is it isn’t quite there yet.”
Witte wrote a commentary that accompanied the DeCode study published today in the journal Science Translational Medicine.
Prostate cancer is the most-common nonskin malignancy in U.S. men and the second-most-frequent cause of death from malignancy, according to the American Cancer Society. This year, about 221,000 men will be diagnosed with prostate cancer in the U.S. and 33,000 will die of it. More than 1 million U.S. men are living with prostate cancer, the society estimates.
DeCode, working with colleagues at universities in Europe and the U.S., scanned the genomes of 15,757 Icelandic men and 454 British men who had taken PSA tests. They identified six genetic changes, each involving an alteration of just one letter of genetic code, which influenced the PSA levels of the men.
When the research team evaluated men who had tissue samples taken from their prostates to look for cancer, they found that four of the genes appeared to increase the likelihood of an elevated PSA score even when no cancer could be found. When these results are considered alongside tests for 23 other gene variations known to increase the risk of prostate cancer, it further boosts the predictive power of the PSA scan, Kari Stefansson, DeCode’s chief executive officer, said in a statement.
The data reported today “enable us to personalize PSA thresholds, thereby changing the recommendation on whether to biopsy for a substantial number of men,” Stefansson said.
Previous studies have estimated that about 10 percent to 20 percent of men getting PSA tests show elevated scores and are recommended for biopsies, tissue samples that let doctors look for the presence of cancer, Witte wrote in the commentary. Of those getting biopsies, about 20 percent to 30 percent get a diagnosis of cancer because high PSA can also be caused by other noncancer conditions and individual genetics.
While the DeCode analysis made PSA test results somewhat more accurate, more improvements will be needed “before it’s ready for prime time,” said Brawley of the Cancer Society. “This is an initial step. It’s going to be tweaked and improved over the next several years.”
The American Urological Association recommends doctors offer regular screening for men starting at age 40. Other groups, including the Cancer Society, don’t make a blanket recommendation, calling for men to consult with their doctors about their risks for cancer and the benefits and drawbacks of PSA tests.
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