By Jillian Foglesong Stabile, MD, FAAFP, DABOM

Genetic Screening for Prostate Cancer: What You Need to Know

Genetic screening for prostate cancer is becoming a key tool in personalizing prevention, diagnosis, and treatment strategies, especially for those with a family history of cancer. While prostate cancer is one of the most common cancers among men, it’s now understood that inherited gene mutations can significantly influence an individual’s risk of developing aggressive or early-onset forms of the disease.

Whether you or a loved one has been diagnosed with prostate cancer, or you're concerned due to family history, genetic testing can offer clarity, and potentially life-saving guidance.

What Is Genetic Screening for Prostate Cancer?

Genetic screening is a type of medical test that looks for inherited mutations in specific genes known to increase the risk of prostate cancer. This is different from tumor testing, which looks at mutations within cancerous tissue. Genetic screening focuses on germline mutations, those passed from parent to child.

Understanding these mutations can help assess your risk of developing prostate cancer or other hereditary cancers and may influence treatment choices if you’ve already been diagnosed.

Who Should Consider Genetic Testing?

According to the National Comprehensive Cancer Network (NCCN), genetic testing is recommended for men with:

• A personal or family history of metastatic, high-risk, or castrate-resistant prostate cancer
• A family history of multiple cancers (e.g., breast, ovarian, pancreatic, or colorectal)
• Known hereditary cancer syndromes such as BRCA1/BRCA2 mutations or Lynch syndrome
• African American ancestry with a family history of prostate cancer, due to elevated risk profiles

Testing is also suggested for men diagnosed with prostate cancer who are considering targeted therapies such as PARP inhibitors, which are more effective in the presence of certain gene mutations like BRCA2.

Which Genes Are Involved?

Several inherited mutations have been linked to an increased risk of prostate cancer. The most well-known include:

• BRCA1 and BRCA2: Most often associated with breast and ovarian cancer, BRCA2 in particular is also linked to more aggressive prostate cancer.
• HOXB13: Associated with early-onset prostate cancer in some families.
• ATM, CHEK2, PALB2: Tumor suppressor genes involved in DNA repair pathways.
• Lynch Syndrome genes (MSH2, MSH6, MLH1, PMS2): Known to increase risks for colorectal and other cancers, including prostate cancer.

What Can Your Test Results Tell You?

A positive genetic test result indicates that you carry a mutation linked to increased cancer risk. This doesn't guarantee you'll develop prostate cancer, but it provides a clearer picture of your genetic susceptibility.

Results can:

• Help tailor treatment strategies if you're already diagnosed
• Influence screening intervals and protocols
• Inform family members, who may also consider testing
• Prompt consideration of preventive strategies or clinical trial enrollment

On the other hand, a negative result means no mutations were found in the tested genes, but it doesn’t completely eliminate the risk of cancer. Sometimes results return as “variants of uncertain significance,” which require careful interpretation by a genetic counselor.

Benefits of Genetic Testing

• Personalized treatment: Men with BRCA2 mutations may benefit from specific drugs (e.g., olaparib) not otherwise prescribed.
• Informed family planning: Identifying a mutation allows relatives to understand their risks.
• Early detection: Men at higher risk may begin screening earlier and more frequently.
• Clinical trial access: Eligibility for cutting-edge treatment options can depend on genetic profiles.

Limitations to Keep in Mind

While the insights from genetic testing are valuable, there are limitations:

• Not all mutations are well understood - some may be classified as “uncertain significance.”
• Psychological impact: Learning you carry a cancer-linked mutation can be emotionally challenging.
• Privacy concerns: While laws like GINA (Genetic Information Nondiscrimination Act) provide protection, some individuals worry about insurance or employment implications.

Cost of Genetic Testing

The cost of genomic testing for prostate cancer varies widely depending on the provider, the number of genes tested, and insurance coverage. Typically, the range is between $250 and $3,500.

Fortunately, many insurance plans now cover testing, especially for individuals who meet established clinical criteria. Some labs and at-home testing platforms offer cash-pay discounts or patient assistance programs.

How Genetic Testing Fits into a Broader Screening Plan

Genetic testing is not a substitute for traditional prostate cancer screening tools like PSA tests and digital rectal exams (DREs). However, it can inform how frequently those screenings should occur and whether to begin earlier.

For example, men with BRCA2 mutations may need PSA screenings starting at age 40 or earlier, while others may follow more general guidelines.

If a hereditary mutation is found, testing of first-degree relatives (parents, siblings, children) is often recommended through a process called cascade testing.

FAQs: Common Questions About Prostate Cancer Genetic Screening

What is genetic screening for prostate cancer?
It’s a test that looks for inherited mutations in genes like BRCA2 and HOXB13 that increase your risk for prostate cancer.

What genes are commonly involved in hereditary prostate cancer?
BRCA1, BRCA2, HOXB13, ATM, CHEK2, and mismatch repair genes such as MSH2 and MSH6.

If I test positive, does that mean I will get cancer?
Not necessarily. It means your risk is higher, but many people with mutations never develop cancer.

Can my family members be affected by my results?
Yes, if you have a mutation, your blood relatives may also carry it and benefit from testing.

How Everlywell Can Help

Everlywell provides accessible, at-home testing kits that help you explore genetic markers associated with various health risks, including cancer. Our tests are easy to use, confidential, and reviewed by independent board-certified physicians.

After you receive your results, you can speak with a licensed provider to interpret your findings and decide on next steps. While Everlywell’s tests are not diagnostic for prostate cancer, they can provide valuable information to discuss with your healthcare provider and may complement more extensive testing when necessary.

References

1. American Cancer Society. Genetic Testing and Counseling for Prostate Cancer Risk.
2. National Cancer Institute. Genetics of Prostate Cancer (PDQ)–Health Professional Version.
3. Mayo Clinic. Prostate Cancer, Family History, Genetics, and Your Risk.
4. de Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020;382(22):2091-2102.
5. Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA Mutations on Metastatic Relapse and Cause-Specific Survival After Radical Treatment for Localised Prostate Cancer. Eur Urol. 2015;68(2):186-193.
6. Ewing CM, Ray AM, Lange EM, et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012;366(2):141-149.
7. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016;375(5):443-453.
8. Giri VN, Knudsen KE, Kelly WK, et al. Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020;38(24):2798-2811.
9. Fulgent Genetics. Comprehensive Cancer – Prostate.
10. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Prostate.
11. National Cancer Institute. Genetic Testing for Hereditary Cancer Syndromes.
12. Centers for Disease Control and Prevention (CDC). Genetic Testing for Hereditary Breast and Ovarian Cancer.
13. U.S. Department of Health & Human Services. Genetic Information Nondiscrimination Act of 2008 (GINA).