Scientists from NorthShore University HealthSystem, the John Hopkins University School of Medicine and Fudan University in China have learned that men with inherited mutations in three genes associated with the development of prostate cancer are more likely to develop aggressive forms of the disease and die from prostate cancer at an earlier age than those without the mutations.
"The study results have an important translational impact because they clearly demonstrate germline mutations in these three well-established genes can be used to predict risk for lethal prostate cancer and time to death," said Jianfeng Xu, MD, DrPH, Vice President of Translational Research at NorthShore. "This confirms major findings from previous studies and provides further direct evidence of the important role of genetic testing in prostate cancer screening and treatment."
The research was a retrospective case study of 313 patients with lethal prostate cancer and 486 with indolent prostate cancer in men of European American, African American and Chinese ancestry.
"Our aim is to find genetic markers among men who are at high risk of developing an aggressive prostate cancer," said Dr. Isaacs,fromthe Johns Hopkins Brady Urological Institute and member of the Johns Hopkins Kimmel Cancer Center. "Mutations in these genes, particularly BRCA2 and ATM, have been linked to aggressive prostate cancer, and this study provides important estimates of the frequency of mutations in men dying at different age ranges."
The research showed that the frequency of gene mutations in lethal prostate cancer patients was meaningfully higher than that observed in localized cancer patients. Mutation carrier status was also significantly associated with more advanced prostate cancer at time of diagnosis, and among lethal prostate cancer patients an earlier death. Moreover, the median survival time after diagnosis was significantly shorter in carriers (four years) than the non-carriers (eight years). In contrast, no mutations were observed in 49 men dying from prostate cancer over the age of 80.
The researchers noted that the results have important clinical implications, and recommend that mutation carrier status be included as an important factor as clinicians make treatment decisions. Men who have their prostates removed may experience significant side effects, including erectile dysfunction and incontinence.
"We have made great progress in identifying molecular factors in the development of prostate cancer in recent years but what remains elusive is being able to distinguish cancers that are particularly aggressive versus ones that are likely to remain indolent, maybe for years," said Brian Helfand, MD, a NorthShore urologist and an author of the study. "This is absolutely vital information to have when considering whether to aggressively treat a patient's cancer or take an approach of active surveillance."
The study was published in European Urology.