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Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity a...

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Autores principales: Vietri, Maria Teresa, D’Elia, Giovanna, Caliendo, Gemma, Resse, Marianna, Casamassimi, Amelia, Passariello, Luana, Albanese, Luisa, Cioffi, Michele, Molinari, Anna Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038462/
https://www.ncbi.nlm.nih.gov/pubmed/33916521
http://dx.doi.org/10.3390/ijms22073753
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author Vietri, Maria Teresa
D’Elia, Giovanna
Caliendo, Gemma
Resse, Marianna
Casamassimi, Amelia
Passariello, Luana
Albanese, Luisa
Cioffi, Michele
Molinari, Anna Maria
author_facet Vietri, Maria Teresa
D’Elia, Giovanna
Caliendo, Gemma
Resse, Marianna
Casamassimi, Amelia
Passariello, Luana
Albanese, Luisa
Cioffi, Michele
Molinari, Anna Maria
author_sort Vietri, Maria Teresa
collection PubMed
description Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.
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spelling pubmed-80384622021-04-12 Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention Vietri, Maria Teresa D’Elia, Giovanna Caliendo, Gemma Resse, Marianna Casamassimi, Amelia Passariello, Luana Albanese, Luisa Cioffi, Michele Molinari, Anna Maria Int J Mol Sci Review Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed. MDPI 2021-04-04 /pmc/articles/PMC8038462/ /pubmed/33916521 http://dx.doi.org/10.3390/ijms22073753 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Vietri, Maria Teresa
D’Elia, Giovanna
Caliendo, Gemma
Resse, Marianna
Casamassimi, Amelia
Passariello, Luana
Albanese, Luisa
Cioffi, Michele
Molinari, Anna Maria
Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title_full Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title_fullStr Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title_full_unstemmed Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title_short Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
title_sort hereditary prostate cancer: genes related, target therapy and prevention
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038462/
https://www.ncbi.nlm.nih.gov/pubmed/33916521
http://dx.doi.org/10.3390/ijms22073753
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