Inherited mutations in three genes predict for aggressive prostate cancer

December 15, 2016

A study of three genes associated with the development of prostate cancer found that men with inherited mutations in these genes 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 to be published in the journal European Urology looked at germline mutations in the ATM and BRCA1/2 genes and represents important progress on the goal of being able to predict which men are more likely to develop a lethal form of prostate cancer versus an indolent one.

"The study results have an important translational impact because they clearly demonstrate in these three well-established genes can be used to predict risk for lethal and time to death," said Jianfeng Xu, MD, DrPH, Vice President of Translational Research at NorthShore University HealthSystem (NorthShore) and Director of the Program for Personalized Cancer Care. "This confirms major findings from previous studies and provides further direct evidence of the important role of genetic testing in and treatment."

The study was a collaboration of NorthShore, the John Hopkins University School of Medicine (William Isaacs, PhD, et al.), and Fudan Institute of Urology, Fudan University (Qiang Ding, MD, et al.), in Shanghai, China. It is 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, the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology at the 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 study found the frequency of gene mutations in lethal prostate cancer patients (6.07%) was significantly higher than that observed in localized cancer patients (1.23%). Mutation carrier status was also significantly associated with more advanced prostate cancer at time of diagnosis, and among lethal prostate an earlier death (67 years vs. 72 years in non-carriers). In addition, 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.

Study authors say 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 incontinence and erectile dysfunction.

"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."

Authors acknowledged the rate of in these three genes in men with lethal prostate cancer is relatively low, pointing to the need for further studies that investigate other DNA repair genes. Members of this same research group have conducted similar such studies and recently had a letter published in the New England Journal of Medicine about the potential role of the DNA repair gene CHEK2 in prostate cancer and lethal prostate cancer.

Explore further: New findings concerning hereditary prostate cancer

Related Stories

New findings concerning hereditary prostate cancer

July 11, 2016
It is a well-known fact that men with a family history of prostate cancer run an increased risk of developing the disease. The risk for brothers of men with prostate cancer is doubled. But a doubled risk of what, exactly? ...

AUA: BRCA mutations may play role in prostate cancer

May 10, 2016
(HealthDay)—A man's risk of aggressive and fatal prostate cancer may be heavily influenced by gene mutations previously linked to breast and ovarian cancer in women, a trio of new studies suggests. Findings from the studies ...

Marker for aggressive prostate cancer doubles up as a drug target

November 8, 2016
Researchers have discovered that a marker found on aggressive prostate cancer cells could also be used as a way to guide treatments to the cancer, according to new research presented at the National Cancer Research Institute ...

Testing for inherited mutations could benefit men with advanced prostate cancer

July 6, 2016
Inherited mutations in genes that function to repair DNA may contribute to metastatic prostate cancer more than previously recognized, according to a study out today in the New England Journal of Medicine. Though infrequent ...

MRI feasible for predicting prostate CA in unselected sample

July 18, 2016
(HealthDay)—Prostate multiparametric magnetic resonance imaging (MRI) is feasible for predicting prostate cancer in an unselected sample of the general population, according to a study published in the August issue of The ...

Prostate cancer tied to higher colorectal cancer risk

March 1, 2016
(HealthDay)—The risk of colorectal cancer is increased after a diagnosis of prostate cancer, according to a study published online Feb. 25 in Cancer.

Recommended for you

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.