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Prostate cancer detection is more accurate if underlying genetic variation is accounted for during PSA screening.
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Incorporating Polygenic Scores in Prostate Cancer Screening

Genetically adjusted PSA levels are more accurate for prostate cancer diagnosis

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Zahraa Chorghay, PhD

Zahraa Chorghay, PhD, is Today's Clinical Lab's clinical writer/editor.

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Published:Apr 19, 2022
|1 min read

A polygenic score adjustment for prostate-specific antigen (PSA) screening could significantly increase the accuracy of prostate cancer detection. According to data presented at the American Association for Cancer Research (AACR) last week, by considering the underlying genetics of the individual, the PSA polygenic score can account for 7–10 percent of the variation in baseline PSA levels.

The use of PSA levels as a biomarker for prostate cancer lacks high specificity and sensitivity, often leading to both the overdiagnosis and underdiagnosis of more aggressive tumors. The researchers hypothesized this can be addressed by understanding the genetic variation for baseline PSA levels unrelated to cancer. 

Kachuri et al. discovered 129 genetic variants associated with baseline PSA levels when they conducted the “largest ever genome-wide association study (GWAS) of PSA in men without prostate cancer” in more than 95,000 men from the United States, United Kingdom, and Sweden. A polygenic score based on these variants then grounds the clinical interpretation of PSA levels. Depending on this genetic variation, the PSA levels needed for a cancer diagnosis are different for each individual.

The researchers showed that the genetically adjusted PSA score would have avoided 21 percent of biopsies that tested negative for cancer. Furthermore, the corrected PSA levels were more robustly associated with aggressive pancreatic cancer.  

Moving forward, the researchers would like to further diversify the cohort they studied and hope to see their polygenic score incorporated into PSA screening to reduce unnecessary biopsies and improve detection of aggressive prostate tumors.