Inherited TP53 variants and risk of prostate cancer

European UrologyMaxwell KN, Cheng HH, Powers J, et al. | December 03, 2021


Findings demonstrate that gTP53 (germline TP53 pathogenic and likely pathogenic variants) predisposes to aggressive prostate cancer. Considering prostate cancer as part of Li-Fraumeni syndrome (LFS) screening protocols and TP53 in germline prostate cancer susceptibility testing is recommended.

  • In this multi-institutional retrospective study, prostate cancer incidence in a cohort of LFS males and gTP53 prevalence in a prostate cancer cohort was assessed to know if gTP53 predisposes to prostate cancer.

  • Among 163 adult LFS males, 31 prostate cancer cases were found.

  • Of LFS males without prostate cancer (n=117) at the time of genetic testing, six received a diagnosis of prostate cancer over a median of 3.0 yr of follow-up, a 25-fold elevated risk.

  • In the prostate cancer cohort, 0.6% had gTP53, a relative risk 9.1-fold higher than that of population controls.

  • Experts noted hotspots at the sites of attenuated variants not related to classic LFS.

  • Somatic inactivation of the second TP53 allele was found in two-thirds of available gTP53 prostate tumors.

  • In gTP53 prostate cancer cases, median age at diagnosis was 56 yr, Gleason ≥8 tumors were present in 44%, and advanced disease at diagnosis in 29%.

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