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Abbott Diagnostics

Genome Study Strengthens Value of PSA Screening as Diagnostic Tool

By Labmedica International staff writers
Posted on 14 Feb 2017
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Image: A structural model of human prostate specific antigen (PSA) with bound substrate complexed with antibody (Photo courtesy of Wikimedia Commons).
Image: A structural model of human prostate specific antigen (PSA) with bound substrate complexed with antibody (Photo courtesy of Wikimedia Commons).
Results of a genome-wide association study (GWAS) of prostate specific antigen (PSA) may lead to improvements that will increase the usefulness of measuring this biomarker for diagnosis of prostate cancer.

Prostate-specific antigen (PSA, also known as kallikrein III, seminin, semenogelase, gamma-seminoprotein and P-30 antigen) is a 34,000 molecular weight glycoprotein produced almost exclusively by the prostate gland. Prostate cancer can cause disruption of the prostate’s cellular architecture, which in turn can result in PSA leaking into circulating blood. PSA screening for prostate cancer has been used for over 20 years, but its use has declined recently because of concerns about over-diagnosis and over-treatment. This is because PSA levels can also be affected by benign prostatic hyperplasia (BPH), local inflammation or infection, prostate volume, age, and germline genetics.

Seeking to strengthen the foundations of the PSA assay, investigators at the University of California, San Francisco and colleagues at Kaiser Permanente performed a genome-wide association study (GWAS) involving 28,503 men from the Kaiser Permanente cohort and 17,428 men from additional replication cohorts, in the aggregate representing nearly half a million PSA tests going back to the 1990s.

The investigators reported that they detected 40 genome-wide significant single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also prostate cancer-associated), and six previously identified for prostate cancer only. Further analysis incorporating prostate cancer cases suggested that at least half of the 40 SNPs were PSA-associated independent of prostate cancer. The 40 SNPs explained 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explained an additional 31.7%; this percentage was higher in younger men, supporting the genetic basis of PSA levels.

These findings provide important information about genetic markers for PSA that may improve prostate cancer screening, thereby reducing over-diagnosis and over-treatment.

"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," said senior author Dr. John Witte, professor of epidemiology, biostatistics, and urology at the University of California, San Francisco. "Disturbingly, some of the cases that are detected are now being diagnosed at a later stage, making successful treatment less likely. It is a big conundrum for the field. Despite the flaws of PSA testing, it does have value as a diagnostic tool. If we want to improve PSA as a useful diagnostic, we need to fold personalized genetics into medical decision-making. We need to be able to tell patients - this is a high PSA value for you, not just for the average person."

The study was published in the January 31, 2017, online edition of the journal Nature Communication.


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