Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention

• Published in: International journal of molecular sciences 2021-04, Vol.22 (7), p.3753
• Main Authors: Vietri, Maria Teresa, D'Elia, Giovanna, Caliendo, Gemma, Resse, Marianna, Casamassimi, Amelia, Passariello, Luana, Albanese, Luisa, Cioffi, Michele, Molinari, Anna Maria
• Format: Article
• Language: English
• Subjects: Biomarkers; BRCA1 protein; BRCA2 protein; Breast cancer; Chromosomes; Cytotoxicity; DNA damage; Family medical history; Genes; genetic testing; Genomes; genotype–phenotype correlation; Germ-Line Mutation; hereditary prostate cancer; Heritability; Homologous recombination; Homology; Humans; Immunotherapy; Male; Metastasis; Mismatch repair; MLH1 protein; Molecular Targeted Therapy; MSH2 protein; MSH6 protein; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Ovarian cancer; Poly(ADP-ribose) polymerase; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - prevention & control; Review; Ribose; Risk analysis; Risk factors; surveillance; Tumor cell lines
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22073753

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 ( , , , and ) and homologous recombination genes ( , , , ). Additional genes are also recommended to be integrated into specific research, including , and . Importantly, and 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.