Genetics a factor in PSA levels

Genetics causes some men to test higher on the blood test for prostate cancer – even when they don’t have the disease – report researchers from Wake Forest University Baptist Medical Center and colleagues in the July 16 issue of the Journal of the National Cancer Institute.

The discovery could lead to more accurate testing and fewer unnecessary biopsies, said Scott D. Cramer, Ph.D., lead researcher, from Wake Forest.

“Up to 20 percent of men may have genetic variants that cause levels of prostate specific antigen (PSA) that are about 30 percent higher than other men, which could result in needless biopsies,” said Cramer. The research was in collaboration with St. Louis University and Washington University School of Medicine.

The PSA blood test, which measures a protein made by prostatic cells, is the most widely used marker to screen for prostate cancer. Cramer, an assistant professor of cancer biology, said the new findings potentially could lead to changes in how PSA results are interpreted and which men are referred for biopsies.

“Further research will be needed to determine how this genetic marker can contribute to making PSA a more accurate screening tool,” said Cramer. “Because of the huge importance of accurately diagnosing prostate cancer, we need to find the best way to use PSA to determine who has prostate cancer and who doesn’t.”

The researchers analyzed blood samples from 405 white males, with a mean age of 63.7 years, who were part of a study looking at asbestos exposure. The researchers excluded men with prostate cancer. Using DNA sequencing, the researchers identified three variations in part of the gene that controls PSA levels. They found that the variations together contributed to a 30 percent increase in PSA levels. Their analysis suggests that if a man has one variation, he has all three. Approximately 20 percent of the study subjects had the variants.

Testing for the variants is quick and inexpensive, said Cramer, and could one day become part of the PSA screening process.

“If a man has the genetic variants, for example, perhaps he would have a higher PSA cutoff before a biopsy is recommended,” said Cramer.

Cramer said additional research should focus on black men, who are known to have higher PSA levels and a greater risk for developing prostate cancer than white men, to see if they have the same variants as the study group.

In addition to race, other factors known to influence PSA levels include age and the presence of non-cancerous prostate disease. The research by Cramer and colleagues is the first to identify specific genetic variants that are responsible for genetic differences in PSA levels. “We’ve known that age, race and disease can influence PSA levels,” said Cramer. “Now, we can add genetics to the list.”

Currently, many physicians recommend biopsies when PSA levels are greater than 4 nanograms per milliliter (ng/ ml). However, there is considerable controversy about cutoffs, said Cramer.

In the study, which excluded men with prostate cancer, PSA levels ranged from .2 to 20 ng/ml. The group of men with the genetic variants that raised PSA had mean levels of 2.0 ng/ml. The other men had mean levels of 1.5 ng/mg. Cramer is conducting additional research to learn if the genetic variants may contribute to prostate cancer development.

“PSA has a biological role in the prostate – to digest proteins,” said Cramer. “It has been shown that PSA can process proteins that are important for prostate growth. One hypothesis is that the higher PSA levels caused by the genetic variants may contribute to prostate cancer development, which would make testing for the variant even more important in the screening process.”

Prostate cancer is the most common type of cancer found in American men, other than skin cancer, and is the second-leading cause of cancer death in men, exceeded only by lung cancer.