Background/aim: Prostate cancer (PCa) is one of the most common tumors in men accounting for the 7.3% of all cancer-associated diseases in 2020. In advanced stage, this pathology is a lethal disease and is the fifth cause of cancer death in men worldwide. The diagnosis of PCa is performed by prostate-specific antigen (PSA) detection combined with direct rectal examination (DRE). However, high PSA levels can be detected in non-malignant conditions leading to overtreatment of non-oncological patients. Moreover, PSA levels are not associated with disease progression; therefore, the research of novel biomarkers could improve diagnosis and prognosis of this tumor. In this regard, genetic polymorphisms may affect PCa outcome as well as to be associated with cancer familiarity. In fact, germline variations detected in different genes including BRCA1, BRCA2, ATM and HOXB13 seem to be associated with PCa susceptibility and progression.

Materials and methods: Somatic and germline polymorphisms were detected by next generation sequencing (NGS) in 48 PCa subjects and paired controls. Gene variants were matched with patient outcome and cancer familiarity to identify mutations linked to prognosis and tumor predisposition.

Results: NGS sequencing has allowed to identify different genetic polymorphisms that could be linked to cancer outcome and predisposition. In particular, somatic and germline mutations found in ATM, FOXA1 and SPOP genes correlate with poor prognosis and/or high Gleason score. Moreover, germline variants lying mainly in ATM, but also in ZFHX3, SPOP, CHD1, CDK12 and APC seem to be associated with hereditary-predisposing cancer syndrome.

Conclusion: Variants correlating with poor prognosis and cancer susceptibility could be usable as possible tumor biomarkers in prostate cancer.

Keywords: Prostate cancer; genetic polymorphisms; next generation sequencing; prognosis; susceptibility.

Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.