Genetics

A familial clustering similar to breast and colon cancer has been reported in prostate cancer (1):

• 5%-10% of all cases of prostate cancer are thought to be primarily due to high risk inherited genetic factors or prostate cancer susceptibility genes (1)

In men with a family history of prostate cancer, the risk increases with increasing numbers of first-degree relatives diagnosed with the disease

• 2.5-fold - if the father had prostate cancer
• 3.4-fold if the brother had prostate cancer
• 3.5-fold if there are two first-degree relatives with a history of prostate cancer
• 4.3-fold if the relative was under 60 years of age at diagnosis (2)

Over 70% of prostate cancers have abnormalities at chromosome 8p22 suggesting that there may be a tumour suppressor gene at this location.

Germline mutation of the BRCA2 tumour suppressor gene substantially increases the lifetime risk of developing prostate cancer (PCa)

• in BRCA2-mutation carriers, localized PCa rapidly progresses to metastatic castrate-resistant prostate cancer (mCRPC) with 5-year cancer-specific survival rates of from 50-60% (3,4)
• BRCA2-mutant tumours also exhibit an increased frequency of intraductal carcinoma (IDC), a pathology that predicts adverse outcome in both familial and sporadic PCa (5,6)

Reference:

• (1) National Cancer Institute 2011. Genetics of Prostate Cancer. Introduction
• (2) Prostate Cancer Risk Management Programme Information for primary care; PSA testing in asymptomatic men. Evidence document. NHS Cancer Screening Programmes, 2010
• (3) Castro, E. et al. Effect of BRCA mutations on metastatic relapse and causespecific survival after radical treatment for localised prostate cancer. Eur. Urol. 2015; 68:186-193.
• (4) Castro, E. et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J. Clin. Oncol. 2013; 31: 1748-1757.
• (5) Risbridger, G. P. et al. Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis. Eur. Urol. 2015; 67: 496-503
• (6) Liede, A., Karlan, B. Y. & Narod, S. A. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J. Clin. Oncol. 2004; 22: 735-742