Gene-Based Screening Guidelines for Prostate Cancer: Are We There Yet?
By Angela Ting, PhD & Jenn Lonzer, MA
Putting new research about prostate cancer and genetics into perspective
Prostate cancer is a serious healthcare issue, with an estimated 161,360 new cases reported in the United States in 2017, according to the National Cancer Institute. Prostate cancer is the second leading cause of death from cancer in men. Sometimes, the disease grows very slowly and doesn’t cause many symptoms. Other times, prostate cancer can be quite aggressive. New research suggests that genetic differences in DNA-repair genes exist between men with metastatic prostate cancer and men with localized prostate cancer.
BRCA1/2 Mutations impact men too
Perhaps the most well-known mutation associated with cancer is BRCA1/2, which can be associated with cancers of the breast and ovaries. But an increasing body of evidence finds that these mutations can lead to cancer in men as well. Men with BRCA1/2 mutations have a higher than average lifetime risk for prostate cancer, while those with BRCA2 mutations have an increased risk of developing male breast and pancreatic cancers.
One 2016 study, published in the New England Journal of Medicine, examined the incidence of germline mutations in genes that mediate the DNA-repair process. They found that among men with metastatic prostate cancer, the overall frequency of germline aberrations in DNA-repair genes was 11.8%, compared to 4.6% in men with localized prostate cancer and 2.7% in men with no known cancer diagnosis.
Possible clinical implications
How does this knowledge impact genetic testing recommendations or prostate cancer management standards? Researchers from The University of Washington and Fred Hutchinson Cancer Research Center address this in a commentary published recently in Clinical Genitourinary Cancer. The review highlights that germline mutations occur more frequently in those with metastatic prostate cancer and suggests that it is time to pay attention to genetics in prostate cancer.
New National Comprehensive Cancer Network (NCCN) guidelines published in October 2017 recommend that any man with a personal history of metastatic prostate cancer is a candidate for BRCA1/2 testing.
While more research is needed regarding the roles these germline mutations may play in the development of prostate cancer and how mutational status in these genes should guide prostate cancer screening and surveillance strategies, genetic testing for men diagnosed with metastatic prostate cancer may have the following clinical implications:
- Targeted therapies: Genetic analyses can help providers develop precision medicine strategies that may include PARP inhibitors, which bring about significant responses in metastatic prostate cancer patients with DNA-repair defects and/or platinum-based chemotherapy.
- Risk reduction: Identifying a germline mutation that predisposes someone to cancer (whether male or female) provides important information that can prompt other family members to seek genetic counseling to identify their individual cancer risk and steps that may be taken to reduce their risks.
As guidelines for genetic testing begin to change, research into the barriers clinicians may face in ordering genetic tests may be warranted, such as access to genetic counselors or medical geneticists, insurance coverage, patient education, etc.
Angela Ting, PhD, studies the epigenetics of cancer with a focus on cancers of the colon and prostate. Ting has made groundbreaking discoveries about changes in a specific gene that is involved with cholesterol transport out of cells. She is a member of Lerner Research Institute’s Center of Excellence in Prostate Cancer Research, a collaborative team of Cleveland Clinic’s top researchers and physicians who are working together to cure prostate cancer.