Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer.
Medicina (Kaunas)
; 60(1)2023 Dec 30.
Article
em En
| MEDLINE
| ID: mdl-38256334
ABSTRACT
Background and Objectives:
Germline DNA damage response (DDR) gene mutations correlate with increased prostate cancer (PCa) risk and a more aggressive form of the disease. DDR mutation testing is recommended for metastatic PCa cases, while eligible information about the mutations' burden in the early-stage localized PCa is still limited. This study is aimed at the prospective detection of DDR pathway mutations in cases with localized PCa and correlation with clinical, histopathological, and radiological data. A comparison to the previously assessed cohort of the advanced PCa was performed. Materials andMethods:
Germline DDR gene mutations were assessed prospectively in DNA samples from 139 patients, using a five-gene panel (BRCA1, BRCA2, ATM, CHEK2, and NBN) targeted next-generation sequencing.Results:
This study revealed an almost three-fold higher risk of localized PCa among mutation carriers as compared to non-carriers (OR 2.84 and 95% CI 0.75-20.23, p = 0.16). The prevalence of germline DDR gene mutations in PCa cases was 16.8% (18/107) and they were detected only in cases with PI-RADS 4/5 lesions. BRCA1/BRCA2/ATM mutation carriers were 2.6 times more likely to have a higher (>1) cISUP grade group compared to those with a CHEK2 mutation (p = 0.27). However, the number of cISUP > 1-grade patients with a CHEK2 mutation was significantly higher in advanced PCa than in localized PCa 66.67% vs. 23.08% (p = 0.047).Conclusions:
The results of our study suggest the potential of genetic screening for selected DDR gene mutations for early identification of cases at risk of aggressive PCa.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Imageamento por Ressonância Magnética
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article