Mutations in 3 Cancer Genes May Help to Mark Aggressive Prostate Cancers

Mutations in 3 Cancer Genes May Help to Mark Aggressive Prostate Cancers

Researchers are one step closer to identifying those men at risk of dying from their prostate cancer, having found that mutations in three well-known cancer genes are linked to a worse prognosis.

Although only a small proportion of prostate cancer patients die of the disease, it is currently difficult to predict who they are and offer them appropriate, more aggressive treatment.

The study, “Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death,” was published in the journal European Urology.

To get a better idea of indicators of an aggressive disease course, researchers analyzed medical records of 313 patients with lethal prostate cancer and 486 with indolent, or slow-growing cancer. The men were of European, African-American, and Chinese descent.

“Our aim is to find genetic markers among men who are at high risk of developing an aggressive prostate cancer,” Dr. William Isaacs, PhD, a professor of Urology at the Johns Hopkins Brady Urological Institute and member of the Johns Hopkins Kimmel Cancer Center, said in a press release. Isaacs is one of three senior investigators collaborating on the study.

The team homed in on the three genes — ATM, BRCA1, and BRCA2 — which have already been linked to the risk of developing prostate cancer. They discovered that while the mutation rate in these genes among men with indolent cancers was 1.2 percent, the mutation rate among those with deadly cancers jumped to 6.1 percent.

Those carrying mutations were frequently in more advanced disease stages when diagnosed. In the group that died of their cancer, the presence of mutations was linked to an earlier death, on average by five years — at age 67 versus 72. Having mutations also shortened the time between diagnosis and death by half, to only four years.

“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,  vice president of Translational Research at NorthShore University HealthSystem, director of the Program for Personalized Cancer Care, and a study co-senior author.

Interestingly, among 49 men who were older than 80 when they died from their prostate cancer, the team did not find any mutations.

“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,” said Isaacs.

But while researchers think that screening for the mutations should be incorporated into clinical examinations of prostate cancer patients, they admit that their findings do not provide the entire picture. More research is needed to identify other contributing factors, which would allow more specific targeting of aggressive tumors.

“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 a study co-author.

“This is absolutely vital information to have when considering whether to aggressively treat a patient’s cancer or take an approach of active surveillance.”