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Allele identified that leads to normal values for prostate-specific antigen higher than those for other men

The presence of a certain allele for a gene controlling prostate-specific antigen levels leads to baseline values that are roughly 30 percent higher than those of other men, according to an article in the July 16th issue of the Journal of the National Cancer Institute.

“Up to 20 percent of men may have genetic variants that cause levels of prostate-specific antigen that are about 30 percent higher than other men, which could result in needless biopsies,” said Scott D. Cramer, Ph.D., lead author of the study.

“Further research will be needed to determine how this genetic marker can contribute to making prostate-specific antigen 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 prostate-specific antigen to determine who has prostate cancer and who doesn’t.”

The researchers analyzed blood samples from 405 white males (mean age, 63.7 years) who were part of a study on asbestos exposure and did not have prostate cancer. With use of DNA sequencing, the investigators identified 3 regions of variation in part of the gene that controls blood levels of prostate-specific antigen. The presence of an allele containing the variant sequences was associated with a 30-percent increase in baseline blood level. Further analysis indicated that men with 1 sequence variation have all 3 variations.

In the study sample of white American men, roughly 20 percent of the participants had the allele associated with higher blood levels. Cramer noted that DNA testing for the allele is both quick and inexpensive; in the future, it might become part of the screening process to determine a more individualized ‘normal’ range of blood values.

Cramer said additional research should focus on other racial groups. For instance, black American men are known to have higher antigen levels and an increased risk for prostate cancer relative to white Americans. The research by Cramer and colleagues is the first to identify a specific allele responsible for genetic differences in antigen levels.

In the U.S., many physicians recommend biopsies when antigen levels are higher than 4.0 ng/mL. However, there is considerable controversy about cutoff levels. In the study, antigen levels ranged from 0.2 to 20 ng/mL. The group of men with the allele for higher antigen levels had mean levels of 2.0 ng/mL compared with mean levels of 1.5 ng/mL for the other study participants.

“Prostate-specific antigen has a biological role in the prostate ? to digest proteins,” said Cramer. “It has been shown that [the antigen] can process proteins that are important for prostate growth. One hypothesis is that the higher [antigen] 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.”


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