MODULE 1 of 9

Can prostate cancer be inherited?

• 5-15% of prostate cancer is inherited from genes, passed down in families.
• Inherited cancers are usually due to changes that cause disease (mutations) in genes that are passed down.
• Mutations can be passed from either mother or father to a child. These are called "germline mutations."
• Not everyone who inherits a mutation develops cancer. However, the cancer risk may be higher for those who inherit mutations. Men who carry mutations may have options to improve cancer detection, screening, or reduce the risk for cancer.
• Men with metastatic prostate cancer (which is cancer that has spread outside of the prostate) have higher rates of inherited genetic mutations compared to men with disease that has not spread.

Quiz Questions: Can prostate cancer be inherited?

MODULE 2 of 9

What is genetic testing?

• Genetic testing checks for changes (mutation) in specific genes that are linked to risk of prostate cancer and other cancers. Not all of your genes are tested.
• Genes are like blueprints that help give instructions to the cells in our body.
• Genetic tests for inherited cancer risks can be done with a blood or saliva sample.
• The blood or saliva is sent to a specialized genetic lab to do the tests.
• There is a small chance that the test may miss some mutations due to technical problems.
• The results are sent to your doctor who will talk about them with you.

Quiz Questions: What is genetic testing?

MODULE 3 of 9

What is genetic counseling?

• Genetic counseling is a process of meeting with a professional who specializes in genetic testing for inherited cancer risk so that patients can make an informed decision for genetic testing.
• Genetic counselors are masters-level healthcare professionals specifically trained in genetic assessment for various diseases such as cancer inheritance. They perform the following for patients:
  • Intake of family cancer history, medical history, and prior genetic testing in the family.
  • Discuss options for genetic testing with their patients, along with benefits and risks of genetic testing, for patients to make an informed decision regarding genetic testing.
  • Coordinate genetic testing for patients and coordinate genetic testing of relatives.
  • Provide genetic recommendations to you and your doctor to help with your cancer care.

Quiz Questions: What is genetic counseling?

MODULE 4 of 9

Does family history matter? What are some important family history questions to consider?

• Your family history may tell us more about your risk of cancer, including prostate cancer.
• Cancers in male and female relatives on either side of the family may affect your risk.
• Family history can also tell us about the need for cancer screening for you and your family members.
• Ashkenazi Jewish individuals are more likely to have mutations in the BRCA genes, which are linked to prostate cancer and some other cancers.
• Sometimes it may be difficult to know your family history. You can provide the information that you know during your genetic visit.

• Did you father or brothers have prostate cancer?
• Did you grandfathers on either side (mother’s or father’s side) have prostate cancer?
• Did your uncles or cousins on either side have prostate cancer?
• For each relative with prostate cancer:
  • About what age were diagnosed with prostate cancer (50s, 60s, 70s, 80s?)
  • Did their prostate cancer spread outside the prostate (advanced or metastatic)?
  • Did they die from prostate cancer? If yes, about how old were they?
• Other cancers in your family may also have a genetic link to prostate cancer. These cancers are:
  • Cancers: Breast, ovarian, pancreatic, colon, uterine, upper bowel, kidney, urinary tract, melanoma
  • More information about cancer in your relatives is helpful if you have it, including: the age when they were diagnosed, if they died from cancer (if so, at what age)
  • Again, it is important to consider cancers in male and female blood relatives when discussing family history.

Quiz Questions: Does family history matter? / What are some important family history questions to consider?

MODULE 5 of 9

What are the results I may get from a genetic test?

• Mutation or Pathogenic Variant: A change in your genes that is linked to a disease or condition, such as increased risk of cancer.
  • This may affect recommendations for cancer screening and may also affect cancer treatment options.
  • Family history can be used to give additional advice. If a mutation is found, testing your relatives for the mutation is also recommended.
  • Risks for more than one type of cancer may be uncovered for you and your family. In many cases, we can change how and where we look for early cancers if we know more about the risk.
• Variant of Uncertain Significance (VUS): These are genetic changes where there is currently limited information regarding the effect on cancer risk. In most cases, VUSs are eventually thought to NOT increase cancer risk. Rarely, more data is obtained lending evidence that a particular VUS is actually linked to increased risk for cancer.
  • A VUS result does not impact recommendations for treatment or screening unless it is reclassified to “mutation”.
  • Family history would be used to give you recommendations on your care.
  • For VUS’s, the testing lab may gather more information in the future that will help them know if the VUS either: (A) increases cancer risk or (B) has no effect on cancer risk. If there is enough information to change the VUS category to “increases cancer risk” (in other words, to a "mutation"), you may get updated advice from your doctor.
• Negative: No mutations (pathogenic variants) or variants of uncertain significance (VUS) are found.
  • Since all genes are not tested, this result is does not completely eliminate any genetic reason for cancer risk in you or your family.
  • Your family history can be used to give you advice.

Quiz Questions: What are the results I may get from a genetic test?

MODULE 6 of 9

What are the types of genetic tests? / What do I need to know about the various genetic testing panels?

• You can choose from a few types of genetic tests (also called "panels"):
  • Focused panel: small set of about 5-6 genes for which there is more information. These genes are best understood in connection with prostate cancer and are already in guidelines for testing.
  • Prostate cancer panels: includes the genes best understood plus about 10-15 other genes that might be linked to prostate cancer. There is less understanding of how some of the genes on these panels may contribute to prostate cancer risk or risk for other cancers. Some of the genes also may not have management guidelines to inform your care.
  • Large cancer panels: include genes with and without guidelines and may include genes with limited cancer risk information. These panels can include up to 80 genes.
  • For this study, we will be testing using a large cancer panel of 51 genes. This panel includes genes with strong association to prostate cancer, other genes with lower association to prostate cancer, genes with association to other cancer types, and many other genes that are potentially important in how prostate cancer functions. Several of the genes on this panel do not have current management guidelines.
  • Another type of genetic testing is done on tumors. This is different than inherited cancer testing as described here. Tumor testing is performed to see if genetic changes (mutations) in the tumor may be helpful to identify treatments or clinical trials for prostate cancer. If a mutation is found in a tumor, there is a chance that it may be inherited. This would need to be confirmed with inherited genetic testing.
  • Other genetic tests that are publically available (such as 23andMe) are not the same as medical genetic testing for inherited prostate cancer as is being performed here.
• More than one cancer risk may be found if you go ahead with genetic testing. Your testing may reveal risks for breast, colon, pancreatic, ovarian, uterine, bowel, urinary, or skin cancers.
• If your testing shows one or more gene mutation, your family members (children, brothers and sisters) could share the same inherited gene mutation. They would each have the choice to get their own testing.
• The more genes tested on a panel, the greater the chance of finding variants of uncertain significance.
• Some gene mutations may have importance if you are planning to have children. In some cases, you may want to get additional information to understand possible effect on future children. For example, testing your reproductive partner may be helpful and important in some cases.
• You may learn you have a gene mutation that is linked with prostate cancer risk, but for which there are not specific recommendations for what to do about the risk. This may mean your doctors and you may not have enough information to impact your care.
• You may also choose to not do genetic testing now, and wait until you are more comfortable with the process.

Quiz Questions: What are the types of genetic tests? / What do I need to know about the various genetic testing panels?

MODULE 7 of 9

How often are germline (inherited) mutations found in men with prostate cancer? / Which genes have the highest risk for prostate cancer?

• Inherited genetic changes that are associated with prostate cancer (mutations) are found in about 10-15% of men with prostate cancer that has spread outside the prostate (also called metastatic prostate cancer).
• Men with prostate cancer at a lower stage can also carry inherited mutations, though rates are higher in men with advanced or metastatic prostate cancer.
• Men with a family history of cancers of the prostate, breast, ovary, pancreas, colon, and uterus are more likely to carry inherited mutations.
• The most important gene to know about is BRCA2. It has the highest risk for prostate cancer, and prostate cancers with BRCA2 mutations are more aggressive and more likely to lead to death from prostate cancer. Inherited mutations in this gene are also linked to breast cancer (in both men and women), ovarian cancer, pancreatic cancer, and melanoma, so it is important for families to know about.
• HOXB13 is another gene that is linked with higher risk of developing prostate cancer and at a younger age.
• Men with one of these mutations may have a 3-6 times greater chance (compared to someone who doesn’t have the mutation) of having prostate cancer in their life.
• Other genes also increase risk of prostate cancer, but the risk appears lower than for BRCA2 and HOXB13
  • Some of these other genes are: BRCA1, CHEK2, and NBN. There is also another group of genes called DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM) where prostate cancer risk can be elevated.
  • Some of these genes are also linked to other cancers.
    • BRCA1 is linked with breast cancer (in men and women), ovarian cancer, and pancreatic cancer.
    • CHEK2 is associated with female breast cancer and colorectal cancer.
    • NBN is associated with female breast cancer.
    • DNA mismatch repair genes are part of Lynch syndrome, where families have hereditary risk for colorectal cancer, ovarian cancer, uterine cancer, small bowel cancer, pancreatic cancer, kidney cancer, and urinary tract cancers.

   

  Quiz Questions: What are the types of genetic tests? / What do I need to know about the various genetic testing panels?

MODULE 8 of 9

Are there any risks of doing genetic testing with regards to my insurance?

• In the U.S., the Genetic Information Nondiscrimination Act (GINA) protects people with genetic mutations from discrimination by their health insurance.
  • GINA does not cover the following plans: health insurance for veterans, US military through Tricare, Indian Health Service, Federal Health Benefits Plans. These plans have their own protections, and therefore patients who have these plans need to check with their plan representatives regarding genetic protection before proceeding with genetic testing.
• Individuals who carry mutations cannot be discriminated by their employers.
  • GINA does not apply to: small businesses with less than 15 employees.
• GINA does NOT cover life insurance, long-term care, or disability insurance.
• It is important to understand this and think about your financial plans before you decide whether to get a genetic test.
• There are also state laws that offer protection against genetic discrimination, but they are different from state to state.
• Your genetic test results will become a part of your medical record. Therefore, if asked by law, your doctors would need to share this information with insurance companies.

Quiz Questions: Are there any risks of doing genetic testing with regards to my insurance?

MODULE 9 of 9

What does my genetic test mean for my family?

• If you are found to carry a genetic mutation, there is a chance that your family members could have the same mutation.
• It is important for family members to get their own genetic testing to determine their risk of cancer.
• This would apply to close blood relatives such as parents, siblings and children. It is also important for more distant blood relatives such as aunts/uncles, cousins, and grandparents.
• Relatives should be referred to a genetic counselor to talk about genetic testing and to decide if they want the tests.
• Even if your genetic results are negative or reveal a "variant of uncertain significance," depending on your family history, it may still be important for your relatives to consider genetic testing.

Quiz Questions: What does my genetic test mean for my family?