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 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 were 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,” says Patrick Pilié, MD, 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 prostate cancer patients do not meet the current guidelines to test for genetic cancer heritability,” he says.

Pilié was part of a research team led by Kathleen Cooney, MD, who is now chair of the Department of Internal Medicine at University of Utah Health and a Huntsman Cancer Institute investigator. Cooney performed the work while at the University of Michigan. She proposed a strategy to identify germline mutations 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, such as 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. The researchers found no difference in cancer aggressiveness or age of diagnosis compared to patients without these mutations.

In addition, co–investigator Elena Stoffel, MD, director of the Cancer Genetics Clinic at the 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 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.

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

This result is also beneficial because a class of drugs called PARP 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.