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Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.

Yu Jiang1,2, Travis J Meyers1,2, Adaeze A Emeka3

  • 1Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.

HGG Advances
|January 7, 2022
PubMed
Summary

Genetic factors may predict which men with low-risk prostate cancer (PC) on active surveillance (AS) will switch to active treatment. This research identifies genetic variants and genes associated with AS discontinuation, aiding personalized PC management.

Keywords:
geneticsgenome-wide association studyprostateprostatic neoplasms

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Area of Science:

  • Genetics
  • Oncology
  • Urology

Background:

  • Active surveillance (AS) is a common management strategy for low-risk prostate cancer (PC), aiming to minimize treatment side effects.
  • A significant proportion of men on AS eventually transition to active treatment, necessitating better predictive tools.
  • Prostate cancer has a strong heritable component, suggesting germline genetics may influence disease progression and treatment decisions.

Purpose of the Study:

  • To identify germline genetic factors associated with conversion from AS to active treatment in men with low-risk PC.
  • To explore the utility of genetic risk scores (GRS) in predicting AS discontinuation.
  • To inform personalized management strategies for low-risk PC patients undergoing AS.

Main Methods:

  • A multi-institutional genome-wide association study (GWAS) of 5,222 PC patients initially electing AS.
  • Replication cohorts including 1,139 additional patients were analyzed.
  • Transcriptome-wide association study (TWAS) and analysis of established genetic risk scores (GRS) for PC and prostate-specific antigen (PSA) levels were performed.

Main Results:

  • The GWAS identified 18 genetic variants associated with conversion from AS, with 15 novel associations.
  • TWAS revealed two genes, MAST3 and GAB2, significantly associated with AS conversion.
  • Higher PC GRS and lower PSA GRS were associated with an increased risk of AS discontinuation.

Conclusions:

  • Germline genetics can potentially identify men at higher risk of discontinuing active surveillance for prostate cancer.
  • Genetic information may help individualize the decision between AS and active treatment, as well as tailor monitoring intensity.
  • These findings support the integration of genetic profiling into the management of low-risk PC.