Identifying Prostate Cancer Genetic Mutations

You would think we would have gotten further down the road towards identifying specific inherited genes associated with prostate cancer, but the ugly truth is we're often uncertain about what to look for, let alone test for. But researchers at University of Utah Health have been making a focused and concerted effort to identify genetic mutations that may influence cancer treatment and cancer risk assessment for family members, and have just published their findings.

"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, MD, medical oncology fellow at the University of Texas MD Anderson Cancer Center and part of a research team led by Kathleen Cooney, M.D., chair of the Department of Internal Medicine at U of U Health. "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 prostate cancer patients do not meet the current guidelines to test for genetic cancer heritability."

Pilié's team put together a highly selective study of 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. Their approach was to examine the frequency of harmful germline mutations in the men. This type of mutation originates on either the egg or sperm and become incorporated into the DNA of every cell in the body of the resulting offspring.

The researchers found that 11 percent of the patients had a disease-causing mutation in at least one cancer-predisposing gene. This suggests that these genetic variations contributed to their prostate cancer.

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," said Kathleen Cooney, MD, the lead author.

One of the key takeaways is that the majority of harmful mutations identified were in genes involved in DNA repair. These prevent the the DNA from healing itself, which can lead to a predisposition for cancer.

The findings are consistent with those of other studies that indicated approximately 10 percent of men with advanced prostate cancer harbor a genetic variant associated with increased cancer risk.

The research has been published in the journal Cancer.