Prostate Cancer Genetic Testing

With 5 to 15% of prostate cancer cases estimated to be due to inherited genes, genetics has a relatively strong influence on prostate cancer. Notably, some mutations (e.g. BRCA1 and BRCA2) are associated with increased prostate cancer risk. Testing for genetic markers like these may be recommended in some cases to better manage those at high risk of cancer, as well as optimize treatments for those with advanced prostate cancer.

Genetic testing for prostate cancer can be characterized as either germline or somatic. Germline DNA is found in every cell of your body, including the germ cells (e.g. sperm or egg cells), allowing germline mutations to be passed down from parent to child. Germline tests help identify cancer risk mutations that you were born with. They are also carried out easily, as the tests can rely on less-invasive samples of blood or saliva.

On the other hand, somatic mutations are obtained over time, and are a natural part of aging. They do not occur in the germ cells, and cannot be passed down from parent to child. These mutations arise due to errors with your DNA repair, or exposure to environmental stressors (e.g. radiation or carcinogens) that damages DNA. Somatic testing is conducted on either tumor tissue or blood samples to identify potential treatment options.

The following genes are known as cancer susceptibility genes which are commonly associated with prostate cancer.

Homologous recombination repair (HRR) genes

These genes support a DNA damage repair system to fix double-stranded breaks in DNA. In prostate cancer, the homologous recombination genes associated with risk of hereditary cancer include: BRCA2, BRCA1, CHEK2, ATM, PALB2 and RAD51D.

Mismatch repair (MMR) genes

These genes support a system for recognizing and repairing wrongly placed nucleotides, the building blocks of DNA. In prostate cancer, the mismatch repair genes associated with risk of hereditary cancer are MLH1, MSH2, MSH6 and PMS2.

Target genes in germline testing

As each patient’s needs for testing are different, the US National Comprehensive Cancer Network (NCCN) recommends testing for the following genes as follows:

Testing for increased risk of prostate cancer:

• HRR gene mutations (BRCA2, BRCA1, CHEK2, ATM, PALB2, RAD51D)
• MMR gene mutations (MLH1, MSH2, MSH6, PMS2)
• EPCAM

Testing for increased risk or early onset of family-based prostate cancer:

• HOXB13

Testing for early onset, aggressive prostate cancer with reduced survival:

• BRCA2

Testing for high risk of hereditary breast and ovarian cancer (HBOC) syndrome:

• BRCA1, BRCA2 or ATM

Target genes in somatic testing

If recommended, your doctor can test for the following genes to identify appropriate personalized therapies or clinical trials for you:

• For metastatic prostate cancer: BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, CDK12
• For metastatic castration-resistant prostate cancer: MLH1, MSH2, MSH6, PMS2

Currently, for metastatic castration-resistant prostate cancer, if you have mutations in BRCA1 or BRCA2, you may be eligible for new targeted therapies such as the poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and rucaparib.

Ultimately, while genetic testing is not necessary for all prostate cancer cases, it can help guide the management of your hereditary prostate cancer risk. In the future, it may also play a more important role in introducing new treatment and clinical trial options for advanced metastatic prostate cancer, based on genetic profiling of each tumor’s mutations.

Learn more: Do I Need Genetic Testing for Prostate Cancer?