Prostate Cancer
Genetics

The goal of this section is to provide educational information
about prostate cancer genetics and how genetic testing may
impact screening and management for prostate cancer.
We include a few basics about prostate cancer, inherited
cancer risk, the importance of knowing family cancer history,
the process of genetic counseling and genetic testing,
understanding genetic results, and the impact of genetics
for screening, treatment and clinical trials.  We include some
helpful resources for patients, families, and clinicians.

Dr. Veda Giri from Yale School of Medicine and
Dr. Stacy Loeb from New York University Langone
Health contributed to this section, which was supported
by a grant from the Department of Defense.

What is prostate cancer

  • The prostate is a walnut-sized gland located between the bladder and penis.
  • The main function of the prostate is to make fluid that is a part of semen.
  • In general, cancer happens when normal cells grow too much or do not die off regularly, like they are supposed to. Then, these cells begin to overgrow and can even begin to invade and spread to other organs.
  • Prostate cancer is when this happens to cells in the prostate.
  • Family history can be helpful to determine your risk of prostate cancer and other cancers.
  • About 5-15% of prostate cancer is inherited from genes, passed down in families.

The basics of genetics and inherited cancer risk

  • A gene is the basic unit of heredity. Genes control the functions of our cells, and as human beings we have 20 to 30,000 genes.
  • Some cancers are caused by changes in genes that are passed down through our families.
  • Most cancers are not hereditary and are due to genetic changes that are acquired in a person’s lifetime.
  • Many different factors can increase cancer risk, such as smoking, excessive alcohol intake or viral exposure.
  • A genetic mutation passed from either mother or father to a child is known as a “germline mutation” and can lead to inherited risk for cancer.
  • Lifetime risk for certain cancers in people with inherited mutations is often significantly increased over the general population.
  • Not everyone who inherits a mutation develops cancer, but the cancer risk may be higher.
  • There may be things that a person can do to reduce their risk of developing cancer, such as leading a healthy lifestyle.
  • Specific cancer screening or risk-reducing recommendations may be considered for people with inherited genetic mutations.

Family history

  • Family history is information about which relatives had cancer and what type of cancer.
  • Family history can tell us about the risk of cancer, and the need for cancer screening.
  • Sometimes it may be difficult to know everything about your family history. Do the best you can when collecting details about family history and share this information with your healthcare team.
  • The risk of prostate cancer is higher in people who have a family history of prostate cancer or several other forms of cancer.
  • It is important to think about the family history of cancer in males and females on the mother’s side of the family and the father’s side of the family. This includes breast, ovarian, pancreatic, melanoma, colon, uterine, kidney, and urinary tract cancers.
  • In addition, information on the following is very helpful when thinking about risk for cancer:
    • Cancers in three generations (including grandparents, parents, aunts, uncles, cousins, siblings, children, nieces and nephews).
    • Types of cancers in males and females
    • Features of prostate cancer (Gleason score, stage, other pathologic features)
    • Age of diagnosis of cancers in family members
    • Screening or treatment information for patients or family
    • Age of death from cancer
    • Lifestyle factors in the family (e.g., smoking and alcohol history)
    • Ancestry (e.g., people with Ashkenazi Jewish ancestry have a higher risk of some genes linked to cancer)
    • Genetic test results if testing was performed by a family member

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:
    • Conduct a detailed review 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 their relatives.
    • Provide genetic recommendations to patients and clinicians to help inform cancer care.

Genetic testing

  • Genetic testing is performed to identify genetic mutations, which are changes in the genes that can lead to diseases such as cancer.
  • Testing itself can be performed on a blood sample or a saliva sample.
  • This sample is sent to a qualified clinical genetic testing laboratory to perform the genetic testing.
  • The results of genetic tests are sent back to your doctor or provider, who will discuss what they mean in terms of screening and other recommendations for you and your family.
  • There are different types of genetic tests you can choose from (also called “panels”):
    • Focused panel: small set of about 5-6 genes for which there is the most information about link to prostate cancer. Furthermore, these genes are in guidelines for testing.
    • Prostate cancer panels: includes genes with strong links to prostate cancer plus about 10-15 other genes that might be linked to prostate cancer.
    • Large cancer panels: include genes with and without guidelines and may include genes with limited cancer risk information. These panels can include 80 genes or more.
  • Genetic tests may identify multiple cancer risks for you and your family. Risks for cancers in children may also be found.
  • Genetic conditions may be uncovered where testing of your reproductive partner could be important.
  • Some gene mutations may not have recommendations for screening or management available at the present time.
  • 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. They do not give information on inherited cancer risk in families.
  • Other genetic tests that are publicly available and marketed directly to consumers are not the same as medical genetic testing for cancer.

Understanding Genetic Results

  • There are 3 broad categories of results from genetic tests:
    • 1) 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 and clinical trial options. Family history can be used to give additional advice.
      • If a mutation is found, there is a chance that your family members could have the same mutation. 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 speak to a genetic counselor to talk about their risk and decide if they want genetic testing.
      • 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.
    • 2) Variant of Uncertain Significance (VUS): These are genetic changes without enough information yet to know if they are linked to cancer or not. Most of the time (but not always), these changes are later found NOT to be linked with cancer risk.
      • The more genes that are tested, the greater chance of getting this result.
      • This result should not change the way you are treated.
      • Family history is used to give you advice.
      • The testing lab may gather more information in the future that will help to know if the change 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.
    • 3) Negative: No mutations (pathogenic variants) or variants of uncertain significance (VUS) are found.
      • Since not all genes are tested, this result 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.

Impact of Genetics for Prostate Cancer Screening

  • Genetic results can impact prostate cancer screening strategies and strategies for additional cancer risks associated with genes.
  • Males with a mutation in a gene that is linked with prostate cancer (such as the BRCA2 gene) are recommended to start prostate cancer screening at age 40, which is younger than in the general population. Some guidelines also recommend considering a prostate MRI at age 50 for males with a mutation in the BRCA2 gene.
  • Males with BRCA mutations are also at risk for additional cancers such as pancreatic cancer, male breast cancer, and melanoma, which also require specific screening strategies.
  • Clinical trials are ongoing to determine optimal approaches to screen for prostate cancer based on genetic results. Ask your doctor if you are interested to learn more about clinical trials.

Impact of Genetics for Prostate Cancer Treatment and Clinical Trials

  • Genetic results have had a major impact on the treatment of prostate cancer, particularly when the cancer has spread outside of the prostate (called “metastatic disease”).
  • Mutations in genes such as BRCA2, which are called DNA repair genes, can provide options for therapies that can target these mutations and improve clinical outcomes.
    • For example, some of these therapies, called PARP inhibitors, target cancer cells that carry mutations in DNA repair genes. PARP inhibitors are now approved for treatment of metastatic prostate cancer along the spectrum of care.
    • Other targeted therapies may also be considered based on genetic mutations.
  • Clinical trials are ongoing to determine the best treatment options for patients with prostate cancer based genetic results. Ask you doctor to learn more about available clinical trials.

Helpful Resources for Patients and Clinicians

  • NSGC Website: The National Society of Genetic Counselors (NSGC) is a national organization advancing the practice of genetic counseling and fostering collaboration for equitable access to genetic healthcare. The website offers many resources for genetic information, research, and genetics services locator based on zip code. Website: www.nsgc.org
  • TARGET webtool: This is a genetic education webtool to help make an informed decision for hereditary prostate cancer genetic testing. This self-paced tool will educate you on hereditary cancer testing and help assess your understanding. The tool features 9 short videos discussing the key points about genetic testing, followed by a quick quiz, and can be completed in about 20 minutes. Once you finish, you’ll receive a downloadable certificate. Share this certificate with your healthcare provider or genetics specialist to discuss genetic testing options and get answers to your questions. (Reference: Loeb et al. TARGET: A Randomized, Noninferiority Trial of a Pretest, Patient-Driven Genetic Education Webtool Versus Genetic Counseling for Prostate Cancer Germline Testing. JCO Precis Oncol. 2024 Mar;8:e2300552. doi: 10.1200/PO.23.00552. PMID: 38452310; PMCID: PMC10939575.) Website: https://curebrca.org/resources/target/
  • CASCAID Tool: CASCAID is designed for people who have tested positive for a hereditary cancer gene mutation, and for their families. The tool contains clear information to help understand genetic test results, explore actionable steps to manage hereditary cancer risk, and prepare for informed conversations with healthcare providers and family. The tool is intended to help facilitate conversations about genetic testing in families to promote cascade testing. Website: www.cascaidtool.com.

More Information and Resources for Healthcare Providers

  • Relevant Guidelines: The National Comprehensive Cancer Network (NCCN) provides guidance on genetic testing criteria and management based on genetic results. Website: www.nccn.org
    • Criteria for genetic testing for prostate cancer can be found in the NCCN Breast, Ovarian, Pancreatic and Prostate Guideline, which is regularly updated. Most insurance carriers follow NCCN guidelines for coverage of genetic testing.
    • Recommendations for prostate cancer screening based upon genetic results are also found in the NCCN Guidelines for Prostate Cancer Early Detection.
    • Recommendations for prostate cancer management based upon genetic results are found in the NCCN Treatment Guidelines for Prostate Cancer.
    • Other professional organizations also provide guidance regarding prostate cancer genetic testing, as well as screening and treatment for carriers of pathogenic variants, such as American Urological Association, European Association of Urology and American Society of Clinical Oncology.
  • HELIX Tool: This toolkit gives information to healthcare providers regarding genetic testing for prostate cancer. The toolkit has two major components: Intake Questions and Educational Modules. The Intake Questions include a series of questions to help healthcare providers determine which patients are eligible for prostate cancer genetic testing. The Educational Modules provide summary information regarding key topics and considerations regarding germline genetic testing for prostate cancer. (Reference: Giri et al. Helix: A Digital Tool to Address Provider Needs for Prostate Cancer Genetic Testing in Clinical Practice. Clin Genitourin Cancer. 2022 Apr;20(2):e104-e113. PMID: 35012874.) Website: www.helix.guide.
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