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Related Experiment Video

Updated: Jul 28, 2025

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
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Genetically adjusted PSA levels for prostate cancer screening.

Linda Kachuri1,2,3, Thomas J Hoffmann1,4, Yu Jiang2

  • 1Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Nature Medicine
|June 1, 2023
PubMed
Summary

This study developed a polygenic score (PGS_PSA) to adjust prostate-specific antigen (PSA) levels for genetic variations. Genetically adjusted PSA improves the accuracy of aggressive prostate cancer detection, potentially refining screening strategies.

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Area of Science:

  • Genetics and Genomics
  • Oncology
  • Biomarker Discovery

Background:

  • Prostate-specific antigen (PSA) screening for prostate cancer is controversial due to overdiagnosis of indolent tumors.
  • Genetic factors influence PSA levels independently of cancer, impacting screening accuracy.

Approach:

  • A multi-ancestry meta-analysis of 95,768 men identified 128 genome-wide significant associations for PSA levels.
  • Developed a PSA polygenic score (PGS_PSA) explaining 9.61% of constitutive PSA variation.
  • Evaluated the utility of PGS-adjusted PSA in predicting aggressive prostate cancer and reducing unnecessary biopsies.

Key Points:

  • PGS_PSA can explain a significant portion of non-cancer-related PSA variation.
  • Genetically adjusted PSA demonstrated improved prediction of aggressive prostate cancer (AUC=0.755) compared to unadjusted PSA (AUC=0.738).
  • Incorporating PGS-adjusted PSA alongside a prostate cancer polygenic score further enhanced aggressive disease detection (AUC=0.786).

Conclusions:

  • Adjusting PSA levels using PGS_PSA offers a promising approach to personalize prostate cancer screening.
  • This method could reduce unnecessary prostate biopsies while improving the detection of clinically significant disease.