Germline testing for prostate cancer involves analyzing a person’s DNA to identify inherited genetic changes. These changes, also known as mutations or variants, are present in all cells of the body from birth and are passed down through families. The primary purpose of this testing is to determine if an individual has an increased risk for prostate cancer or if these inherited genetic factors might influence the cancer’s behavior or treatment response.
Germline Versus Somatic Testing
Genetic testing in cancer care broadly falls into two categories: germline and somatic testing. Germline testing focuses on inherited genetic changes, which are present in every cell of the body because they originated from the egg and sperm that formed the individual. These changes are passed down from parents to their children. Identifying germline mutations can reveal a predisposition to certain cancers that runs in families.
Somatic testing, in contrast, examines genetic changes that are acquired during a person’s lifetime and are found only within the cancer cells themselves. These mutations are not inherited and cannot be passed on to offspring. Somatic testing, also known as tumor testing, helps guide treatment decisions by identifying specific alterations in the tumor that may respond to targeted therapies. While germline mutations are present in tumor cells, somatic testing can uncover additional changes unique to the tumor, which influences treatment strategies for the cancer itself.
Why Germline Testing is Important for Prostate Cancer
Identifying inherited mutations can reveal a higher personal risk for prostate cancer, often associated with more aggressive forms or earlier onset of the disease. Mutations in BRCA2 are linked to a 3- to 4-fold increased risk of prostate cancer compared to the general male population, and they are also associated with poorer outcomes. Mutations in BRCA1 also elevate prostate cancer risk, though to a lesser extent than BRCA2.
These inherited mutations also carry implications for the patient’s risk of developing other cancers, such as male breast cancer, pancreatic cancer, and melanoma. For female relatives, these mutations can increase the risk of breast, ovarian, pancreatic, and melanoma cancers. This broader risk assessment helps inform comprehensive screening strategies for the patient and their family.
Germline testing is recommended in several situations:
- A family history of prostate cancer, particularly if it was diagnosed at an early age or was aggressive.
- A family history of other related cancers, such as breast, ovarian, pancreatic, or colorectal cancers, also suggests germline testing.
- Patients with aggressive or metastatic prostate cancer, or those diagnosed with prostate cancer at an early age, are advised to undergo testing.
- Specific prostate cancer pathology features, such as intraductal or cribriform histology, also indicate a higher likelihood of inherited mutations.
The Germline Testing Process and Results
Germline testing involves collecting a sample from non-cancerous cells. This can be done using a blood sample, a saliva sample, or a buccal (cheek) swab. DNA from these samples is analyzed to identify specific genetic changes.
Common genes associated with hereditary prostate cancer risk often included in testing panels are BRCA1, BRCA2, ATM, CHEK2, and HOXB13. Genes linked to Lynch syndrome, such as MLH1, MSH2, MSH6, PMS2, and EPCAM, may also be included, as Lynch syndrome can increase prostate cancer risk. The normal function of many of these genes is to repair DNA errors, which helps protect against cancer development.
Patients generally receive one of three types of results. A “positive” result (also called a pathogenic or likely pathogenic variant) means a mutation known to increase cancer risk was identified. A “negative” result, or “no pathogenic variant identified,” indicates no known disease-causing mutations were found in the genes tested.
The third type is a “Variant of Uncertain Significance” (VUS), meaning a genetic change was found, but its impact on cancer risk is not yet clearly understood. VUS results are common and may be reclassified over time as more scientific information becomes available. A genetic counselor helps patients understand the implications of the testing process and their results.
What Germline Test Results Mean for Treatment and Family
Germline test results have implications for prostate cancer treatment and family members. Identifying specific inherited mutations can lead to targeted therapies. Patients with BRCA1 or BRCA2 mutations, or other DNA repair gene alterations, may be candidates for PARP inhibitors like olaparib or rucaparib, which are approved for metastatic castration-resistant prostate cancer.
These mutations can also indicate a potential benefit from platinum-based chemotherapy. Test results can also determine eligibility for clinical trials investigating new treatments for individuals with certain genetic profiles. In some cases, these results may also influence ongoing surveillance strategies or the intensity of current treatments.
Beyond individual treatment, germline test results impact the patient’s family. If a pathogenic mutation is identified, close relatives can be offered cascade testing to determine if they also inherited the mutation. This knowledge enables personalized cancer risk management strategies for at-risk family members, including earlier or more frequent screenings for prostate cancer, as well as for other associated cancers like breast, ovarian, or pancreatic cancer. Genetic counseling provides information about risks and management options for family members considering testing.