When a patient is said to have a strong family history of PC, it is important to note the number of relatives affected, the degree of familial relation, and their age at diagnosis. True hereditary PC (manifested by approximately 9% of PC patients) is defined as patients with > 3 relatives affected, or > 2 who have developed early onset disease (before 55 years).
There are several genes known to be mutated in PC. These include BRCA1, BRCA 2, ATM, P53, HOXB13, and others. Some of these, like the BRCA2, is associated with a more aggressive disease as well as an earlier onset. It is hypothesized that the 2nd hit hypothesis of tumor suppressor gene inactivation, is what drives the formation of mutations and cancer. In general, the frequency of germline mutations in PC is around 7-9%, however it has been shown that in metastatic patients it is close to 12%.1
Patients that are most at risk for genetic predisposition for PC are those with family history, hereditary syndromes, metastatic disease and early onset. The hereditary syndromes include hereditary breast ovarian cancer (HBOC), Lynch syndrome (hereditary non-polyposis colorectal cancer), and Fanconi anemia.
Nowadays, there is growing usage of various genetic panel tests to try to identify those patients who are at risk for developing hereditary PC. Usage of these tests will allow us to identify these patients at an earlier stage, and personalize treatment.
In summary, knowledge of the associated genetic changes in hereditary PC is required, both of somatic and germline mutations. Understanding these genetic mutations, and applying tests to identify the patients harboring them, will allow us to diagnose these patients at an early stage and personalize their treatment. Certain selected high-risk populations should be tested as soon as possible. These include patients with PC family history, hereditary syndromes, metastatic disease, and early onset disease.
Speaker: Dr. Antonio Alcaraz, Medical Advantage Barcelona
1. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. New England Journal of Medicine 2016; 375(5): 443-53.
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands
Watch: Colin Pritchard on Germline and Somatic DNA in Men with Castration-Resistant Prostate Cancer