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Jianfeng Xu, DrPH, Vice President of Translational Research at NorthShore University HealthSystem, and other physicians and scientists at NorthShore are working to unlock the genetic clues behind prostate cancer. Dr. Xu, who is also Director of the Program for Personalized Cancer Care within the Center for Personalized Medicine at NorthShore, and his team recently came out with a study pointing to three genetic mutations as markers for aggressive prostate cancer.
How do personalized medicine and genetic testing impact prostate cancer care (i.e. screening, diagnosis and treatment)?
At present, the standard for prostate cancer care typically does not include genetic testing. The supplementation of standard care with genetic testing, however, can greatly help personalize decision making. By assessing one’s inherited risk for prostate cancer through genetic testing, physicians are able to more effectively screen for the disease. Effective, targeted screening for prostate cancer is critical, as more treatment options are available when the disease is diagnosed at an earlier stage. Throughout the spectrum of prostate cancer care, from screening to late-stage treatment using chemotherapy, genetic testing of both inherited (germline) DNA and tumor (somatic) DNA can be of great help in reducing mortality. Recent studies have produced more evidence, and should be taken into consideration when deciding whether to undergo genetic testing for prostate cancer-related gene mutations.
What are the latest research developments in this field?
Recent studies have shown that inherited cancer-related mutations in DNA repair pathways are more common in men with prostate cancer than previously thought. In our own study of three such genes (BRCA1, BRCA2 and ATM) published in the journal European Urology, we found that men who inherited a mutation in one or more of these genes were at 5-fold increased risk of developing lethal prostate cancer compared with men who did not have a mutation in any of these three genes. Furthermore, a subset of the men who died of prostate cancer showed an even higher prevalence of these mutations. These findings indicate that mutation carriers are more likely to die of prostate cancer if not caught in the early stages and treated with the proper treatment. We found that this was true of men diagnosed at both early and late stages of the disease. Finally, of the men who harbored these mutations, only 50% had a family history of prostate cancer. This finding suggests that genetic information is more accurate at predicting outcomes than is family history information, which is the current standard of care.
What are the implications of these new developments for prostate cancer care?
Given the findings that having a mutation predicts lethality of prostate cancer at any stage of the disease and patients can be positive for mutations regardless of family history, it is reasonable to suggest that all men diagnosed with the disease should undergo genetic testing. Knowledge of a mutation can be a critical guiding factor in deciding whether to undergo surgery to remove the prostate. Knowledge of a mutation can also help determine which treatment is expected to be the most effective.
Knowledge of a genetic mutation in a gene implicated in prostate cancer is also useful for developing a personalized prostate cancer screening plan in asymptomatic men (e.g. whether, when and how often to undergo PSA testing). Since inherited DNA does not change throughout one’s lifetime, getting a genetic test once can help guide prostate cancer screening throughout the entirety of a man’s adult life.
What more is happening on the research front with prostate cancer?
In addition to genetic testing, we have also developed an algorithm that uses more common, smaller-impact genetic changes called single nucleotide polymorphisms (SNPs). SNPs can be combined in a measure called a Genetic Risk Score (GRS). For men with a GRS in the top 1 percentile of the general population, their risk of developing prostate cancer is nearly 6-fold greater than men with an average GRS.