Nav: Home

Study: Inherited mutations in 3 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 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 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 prostate cancer screening 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 cancer patients 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 mutations 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.
-end-
About NorthShore University HealthSystem

NorthShore University HealthSystem is an integrated healthcare delivery system consistently named among the nation's best. The NorthShore system, headquartered in Evanston, IL, includes four hospitals - Evanston, Glenbrook, Highland Park and Skokie - and is consistently ranked as a Top 15 Teaching Hospital System in the U.S. NorthShore also includes a 900 physician multispecialty group practice, NorthShore Medical Group, located in 100-plus offices across Chicago and many of the Northern Suburbs. NorthShore is a Magnet recognized organization, the first in Illinois designated as an entire system to receive this prestigious honor that demonstrates excellence in nursing and high standards in patient care. The system also supports the NorthShore Research Institute; the NorthShore Philanthropic Foundation; and NorthShore Home & Hospice Services. In addition to launching Be Well Lake County, a community health initiative committed to providing greater access to comprehensive care, NorthShore contributes more than $209 million in charitable care and services to the community it serves.

NorthShore University HealthSystem

Related Prostate Cancer Articles:

ESMO 2020: Breast cancer drug set to transform prostate cancer treatment
A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.
Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.
The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.
Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.
First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
More Prostate Cancer News and Prostate Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.