Abstract
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.
Highlights
Prostate cancer (PCa) is globally the second most diagnosed cancer type in men [1]and the most common cause of cancer-related deaths, with an estimated 1,600,000 cases and366,000 deaths annually [2]
Men with a personal history of Gleason ≥7 PCa with a family history of a Breast cancer type1 (BRCA1)/2 mutation, or one close relative with ovarian or breast cancer at age 3 ng/mL [30]
A more accurate knowledge of the mechanisms of Hereditary prostate cancer (HPCa) predisposition could be brought by individualized PCa screening and treatment
Summary
Prostate cancer (PCa) is globally the second most diagnosed cancer type in men [1]. and the most common cause of cancer-related deaths, with an estimated 1,600,000 cases and. PCa is clinically a very heterogeneous disease; many patients show an aggressive disease with progression and metastasis while other patients show a slow disease with low propensity to progression [2]. HPCa is characterized by an early age onset, an aggressive disease progress and locally advanced stage. Men with a brother or father diagnosed with prostate cancer have a two- to four-fold greater risk of developing PCa [10]. About 170 susceptibility loci for HPCa, accounting for ~33% of familial prostate cancer risks, have been identified with genome wide association studies (GWAS) [13,14].
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