Inherited TP53 Variants and Risk of Prostate Cancer.
Eur Urol
; 81(3): 243-250, 2022 Mar.
Article
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| MEDLINE
| ID: mdl-34863587
ABSTRACT
BACKGROUND:
Inherited germline TP53 pathogenic and likely pathogenic variants (gTP53) cause autosomal dominant multicancer predisposition including Li-Fraumeni syndrome (LFS). However, there is no known association of prostate cancer with gTP53.OBJECTIVE:
To determine whether gTP53 predisposes to prostate cancer. DESIGN, SETTING, ANDPARTICIPANTS:
This multi-institutional retrospective study characterizes prostate cancer incidence in a cohort of LFS males and gTP53 prevalence in a prostate cancer cohort. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
We evaluated the spectrum of gTP53 variants and clinical features associated with prostate cancer. RESULTS ANDLIMITATIONS:
We identified 31 prostate cancer cases among 163 adult LFS males, including 26 of 54 aged ≥50 yr. Among 117 LFS males without prostate cancer at the time of genetic testing, six were diagnosed with prostate cancer over a median (interquartile range [IQR]) of 3.0 (1.3-7.2) yr of follow-up, a 25-fold increased risk (95% confidence interval [CI] 9.2-55; p < 0.0001). We identified gTP53 in 38 of 6850 males (0.6%) in the prostate cancer cohort, a relative risk 9.1-fold higher than that of population controls (95% CI 6.2-14; p < 0.0001; gnomAD). We observed hotspots at the sites of attenuated variants not associated with classic LFS. Two-thirds of available gTP53 prostate tumors had somatic inactivation of the second TP53 allele. Among gTP53 prostate cancer cases in this study, the median age at diagnosis was 56 (IQR 51-62) yr, 44% had Gleason ≥8 tumors, and 29% had advanced disease at diagnosis.CONCLUSIONS:
Complementary analyses of prostate cancer incidence in LFS males and gTP53 prevalence in prostate cancer cohorts suggest that gTP53 predisposes to aggressive prostate cancer. Prostate cancer should be considered as part of LFS screening protocols and TP53 considered in germline prostate cancer susceptibility testing. PATIENTSUMMARY:
Inherited pathogenic variants in the TP53 gene are likely to predispose men to aggressive prostate cancer.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Síndrome de Li-Fraumeni
Tipo de estudio:
Etiology_studies
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Guideline
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Observational_studies
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Risk_factors_studies
Límite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur Urol
Año:
2022
Tipo del documento:
Article