Unravelling genetic predictors that determine a man’s natural PSA levels could help enhance the sensitivity and specificity of PSA tests as a tool for diagnosing prostate cancer, according to a recent study.
Researchers at the University of California San Francisco (UCSF) were able to identify genetic variations that explain up to 41 percent of PSA variation, suggesting that this information could aid in improving prostate cancer screening.
Although PSA tests have been used for more than 20 years to detect and observe prostate cancer, recent studies have shown that the test frequently leads to false positives and unnecessary treatment, and false negatives that give men a false sense of security.
As a result, the U.S. Preventive Services Task Force advised against the use of PSA tests as a diagnostic tool for prostate cancer in 2012. That led to a drop in clinicians’ use of this test.
“In the few years that PSA testing has become less popular, the use of the test has declined and the number of prostate cancer diagnoses has dropped,” John Witte, PhD, a UCSF professor of epidemiology and urology, and co-senior author of the new study, said in a press release. “Disturbingly, some of the cases that are detected are now being diagnosed at a later stage, making successful treatment less likely. It’s a big conundrum for the field.”
One of the biggest problems with PSA tests is that they rely on the measurement of a protein which men produce at different levels. Diseases like benign prostatic hyperplasia, local inflammation or infection, prostate volume, age, and genetic factors can all influence a man’s baseline PSA levels, suggesting that a threshold that applies to all men will necessarily be imprecise.
Researchers believe that determining the genetic basis of PSA levels unrelated to cancer may help increase both the sensitivity and specificity of prostate cancer screening, by adjusting PSA levels to the natural levels predicted by genetics.
Witte and Stephen K. Van Den Eeden, PhD, a research scientist at Kaiser Permanente Division of Research and professor of urology at UCSF, examined data from 28,503 men included in Kaiser Permanente’s long-term data set, and an additional 17,428 men from other independent cohorts.
“The unique setting of Kaiser Permanente allowed us to link every man in the study to our electronic clinical data and determine not just that they had a test, but also the level and frequency of testing over many years,” said Van Den Eeden.
After conducting an extensive genetic analysis, the team was able to identify 40 genetic regions that predicted 9.5 percent of normal variation in PSA levels in healthy men. The remaining genetic regions examined in the study could explain an additional 31.7 percent, though the researchers noted that the tests were not specific enough to determine which particular regions were responsible for such variation.
They believe that further studies may uncover novel genetic predictors of PSA levels, and that such information could be combined with PSA tests to better evaluate test results and more reliably predict a man’s risk of prostate cancer.