From the Guidelines
The germline mutation associated with an increased incidence of early onset high-grade prostate cancer is BRCA2 (option B). This is based on the most recent and highest quality evidence from the NCCN clinical practice guidelines in oncology, version 2.2019 1, which suggests that BRCA2 mutations have been associated with a 2- to 6-fold increase in the risk for prostate cancer, and prostate cancer in men with germline BRCA2 mutations appears to occur earlier, has a more aggressive phenotype, and is associated with significantly reduced survival times than in noncarrier patients. Some key points to consider include:
- BRCA2 mutations confer a higher risk of prostate cancer compared to BRCA1 mutations, with a 2- to 6-fold increase in risk 1
- Prostate cancer in men with germline BRCA2 mutations tends to be more aggressive and is associated with reduced survival times 1
- The NCCN guidelines recommend that men with BRCA2 mutations start prostate cancer screening at age 40 1
- While HOXB13, P53, and MSH2 are associated with other cancer syndromes, BRCA2 has a specific and significant association with early-onset, high-grade prostate cancer 1
- Men with BRCA2 mutations often have a strong family history of prostate cancer and may benefit from earlier screening protocols starting at age 40 rather than the standard age of 50-55.
From the Research
Germline Mutation and Prostate Cancer
- The germline mutation associated with an increased incidence of early onset high-grade prostate cancer is BRCA2, as studies have shown that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age 2, 3, 4, 5.
- BRCA2 mutation carriers have been found to have a higher risk of developing high-grade prostate cancer, with a 3-fold elevated risk compared to non-carriers 5.
- Other genes, such as BRCA1, HOXB13, and DNA repair genes, have also been associated with an increased risk of prostate cancer, but the evidence is not as strong as it is for BRCA2 3, 4, 5.
- Germline testing and genetic counseling have important implications in cancer screening and therapeutic decisions making for patients affected by prostate cancer, particularly those with a positive family history of prostate cancer or men with high risk or metastatic disease 3, 4.
Specific Genes and Prostate Cancer Risk
- BRCA2: associated with a 3-fold elevated risk of high-grade prostate cancer 5 and a 23-fold relative risk of developing prostate cancer by age 56 years from a deleterious germline BRCA2 mutation 2.
- BRCA1: not associated with prostate cancer, but the BRCA1-185delAG mutation was associated with high Gleason score tumors 5.
- HOXB13: associated with an increased risk of prostate cancer, but the evidence is not as strong as it is for BRCA2 4.
- DNA repair genes: associated with an increased risk of prostate cancer, particularly in early-onset cases 3, 4.