Genetic testing for prostate cancer is rapidly increasing, with expanded genetic tests and guidelines. Multiple genes have been found to contribute to prostate cancer risk. In addition, high rates of inherited genetic mutations have been identified in men with metastatic prostate cancer. Genetic tests have expanded to encompass single gene testing, cancer-focused or guidelines-focused testing, and large comprehensive cancer panels. While this provides flexibility in choice of test based on patient preference, men need to understand the benefits and limitations of testing, as well as implications of test results for themselves and their families to make an informed decision about genetic testing.
Genetic counseling is a specialty focused on performing genetic assessment and coordinating genetic testing. A genetic counselor is a trained professional who can educate patients on cancer inheritance, benefits/risks/limitations of testing, and support patients in making informed decisions regarding genetic testing.
A key part of genetic evaluation is assessment of family history of cancers. For prostate cancer risk, it is important for a man to provide information about a range of cancers in family members, particularly cancers of the prostate, breast, ovary, pancreas, colon, uterus, and melanoma since there can be common genetic reasons for these cancers in a family. It is important to consider cancers in men and women on the paternal and maternal sides of the family. Ancestry is also an important part of the family history. Other factors important in the initial assessment include age at diagnosis of cancers, Gleason score of prostate cancer in men and their male relatives, and stage of prostate cancer.
Most genes important in risk for prostate cancer may also confer risk for other cancers. For example, BRCA2 mutations are associated with aggressive prostate cancer and also carry risk for pancreatic cancer, male breast cancer, and melanoma. For women, additional risks include breast cancer and ovarian cancer. Depending on the gene, there may be guidelines for management of cancer risk.
Three types of test results are possible from genetic testing. These include positive for mutation (in which case cancer screening or management are based upon the gene if guidelines are available as well as personal and family history), negative (in which case cancer screening is based upon personal or family history), or variants of uncertain significance (VUS). The more genes that are tested, the higher the chance of uncertain VUS being identified. These VUS do not change management at the time of reporting, but can be reclassified over time to “mutation” or “benign.”
It is important to understand genetic discrimination laws— what they cover and what they do not cover. The Genetic Information Nondiscrimination Act (GINA) is a law that prevents health insurance companies and employers from discriminating against someone based on his or her genetic information. Notable exceptions include health insurance through the military or Veteran’s Affairs, and employment with a company that has fewer than 15 employees. In addition, the law does not include life insurance, disability insurance, and long-term care insurance.
At Sidney Kimmel Cancer Center, we developed the first Men’s Genetic Risk Clinic in the U.S. in 2014 focused on comprehensive genetic counseling and genetic testing for men with prostate cancer or at-risk for prostate cancer linked to the Multidisciplinary Clinic. Our approach of providing men with state-of-the-art genetic counseling and opportunities for multigene testing for prostate cancer have led to novel insights into the mutation spectrum and needs of men undergoing genetic counseling.
Genetic evaluation for inherited prostate cancer is an exciting new area with unique opportunities to expand precision oncology and tailored screening for men and their families.