Researchers propose new approach to identify genetic mutations in men with prostate cancer

June 29, 2017, University of Utah
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Scientists have had limited success at identifying specific inherited genes associated with prostate cancer, despite the fact that it is one of the most common non-skin cancers among men. Researchers at University of Utah Health studied prostate cancer patients with multiple cancer diagnoses, many who would not be recommended for genetic tests following current guidelines, to identify genetic mutations that may influence cancer treatment and cancer risk assessment for family members. Their findings are reported in the June issue of the journal Cancer.

"We commonly use a combination of a patient's personal and family cancer histories to identify those individuals who may have a mutation in a gene that predisposes that individual to developing cancers," said Patrick Pilié, M.D., medical oncology fellow at the University of Texas MD Anderson Cancer Center. "Testing for hereditary cancers impacts not only the patient with cancer but also potentially the cancer screening and health outcomes of their entire family, but many do not meet the current guidelines to test for genetic cancer heritability."

Pilié was part of a research team led by Kathleen Cooney, M.D., chair of the Department of Internal Medicine at U of U Health and a Huntsman Cancer Institute investigator, who proposed a strategy to identify germline in men selected for the study based on their clinical history not their family history.

The study was highly selective, including 102 patients who had been diagnosed with prostate cancer and at least one additional primary cancer, like melanoma, pancreatic cancer, testicular cancer, or Hodgkin lymphoma.

The researchers examined the frequency of harmful germline mutations in this group of men. These mutations originate on either the egg or sperm and become incorporated into the DNA of every cell in the body of the resulting offspring.

Using next generation sequencing, the researchers found that 11 percent of the patients had a disease-causing mutation in at least one cancer-predisposing gene, which suggests these genetic variations contributed to their prostate cancer. Cooney found no difference in cancer aggressiveness or age of diagnosis compared to patients without these mutations.

In addition, a certified genetic counselor and co-investigator Elena Stoffel, M.D., University of Michigan Comprehensive Cancer Center, reviewed personal and family histories from each patient to determine whether they would meet clinical genetic testing guidelines. The majority of the men in the study, 64 percent, did not meet current criteria to test for hereditary cancer based on personal and/or family history.

The findings suggest that there are men with heritable prostate cancer-predisposing mutations that are not eligible for genetic screening under current guidelines.

"This is the first paper in which we can show the potential of using a clinical history of multiple cancers, including prostate cancer, in a single individual to identify inherited germline mutations," Cooney said.

The majority of harmful mutations identified were in genes involved in DNA repair.

"These mutations prevent the DNA from healing itself, which can lead to a predisposition for cancer," Cooney said.

This result is also beneficial because drugs like PARP [poly ADP ribose polymerase] inhibitors have a better success rate in treating cancers with the underlying gene mutation associated with DNA repair.

Cooney cautions that this is a small pilot study rather than a broader epidemiological survey, and it consists of a highly specific subset of patients.

"We cannot generalize these findings to the broader population, because we used highly selective criteria to tip us off to patients that may have mutations outside typical hereditary genetic patterns," she said.

The 102 patients included in the study were identified from the University of Michigan's Prostate Cancer Genetics Project, which registers patients who are diagnosed with prostate cancer before age 55 or who have a first- or second-degree relative with prostate cancer. In addition, the research team identified patients from the University of Michigan's Cancer Genetics Registry, which includes individuals with personal or family history suggestive of a hereditary risk of cancer.

"Our findings are in line with those of other studies, suggesting that approximately 1 in 10 men with advanced prostate cancer harbors a genetic variant associated with increased cancer risk," said Stoffel. "While is an important tool, there may be better ways to identify patients with genetic risk."

Future studies with larger sample sizes will include sequencing of tumors that will allow investigators to more carefully explore the different features associated with tumors that arise in individuals with .

"This approach will help us identify patients at greater risk for aggressive so they can seek earlier screening while pre-symptomatic," Cooney said.

Explore further: Are men with a family history of prostate cancer eligible for active surveillance?

More information: Patrick G. Pilié et al. Germline genetic variants in men with prostate cancer and one or more additional cancers, Cancer (2017). DOI: 10.1002/cncr.30817

Related Stories

Are men with a family history of prostate cancer eligible for active surveillance?

April 6, 2017
Active surveillance—careful monitoring to determine if or when a cancer warrants treatment—is an increasingly prevalent choice for prostate cancer, but it's unclear if the strategy is appropriate for men with a family ...

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 ...

Sequencing prostate tumors from African-American men reveals a novel tumor suppressor gene

May 19, 2017
African-American men develop prostate cancer more often than other men, and it tends to be more deadly for this population. Some of the differences seem to be due to socioeconomic factors, but scientists wondered whether ...

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 ...

Scientists report genetic test to help predict men at most risk from aggressive prostate cancer

March 28, 2017
Scientists are reporting a test which can predict which patients are most at risk from aggressive prostate cancer, and whether they suffer an increased chance of treatment failure. This test, reported at the European Association ...

Recommended for you

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Combining three treatment strategies may significantly improve melanoma treatment

December 12, 2018
A study by a team led by a Massachusetts General Hospital (MGH) investigator finds evidence that combining three advanced treatment strategies for malignant melanoma—molecular targeted therapy, immune checkpoint blockade ...

Researchers use computer model to predict prostate cancer progression

December 12, 2018
An international team of cancer researchers from Denmark and Germany have used cancer patient data to develop a computer model that can predict the progression of prostate cancer. The model is currently being implemented ...

New insight into stem cell behaviour highlights therapeutic target for cancer treatment

December 12, 2018
Research led by the University of Plymouth and Technische Universität Dresden has identified a new therapeutic target for cancer treatment and tissue regeneration – a protein called Prominin-1.


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.