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Inherited genetic mutations found in 12% of men with metastatic prostate cancer

Staff Writer | July 8, 2016
One in nine (12%) men with metastatic prostate cancer carry inherited mutations in DNA damage repair (DDR) genes, reports a new study funded in part by the Prostate Cancer Foundation (PCF).
Prostate cancer
Genetics   The implications are profound
These practice-changing findings suggest that all metastatic prostate cancer patients should undergo screening for DDR defects, and that families of men found to have these mutations seek genetic counseling.

"The implications of these groundbreaking findings are profound," said Jonathan W. Simons, MD, president and CEO, Prostate Cancer Foundation.

"Not only will they advance precision medicine for prostate cancer by identifying who may benefit from targeted treatment, but also new recommendations for screening can help determine who is at the greatest risk for this disease so we can intervene. Also, we estimate more than 12,000 U.S. families facing prostate cancer are carrying these genes in their children and grandchildren."

"I think every man today with metastatic prostate cancer should have genetic testing, regardless of age or family history," said Peter Nelson, MD, of Fred Hutchinson Cancer Research Center, and Professor of Medical Oncology at the University of Washington and the Genitourinary Oncology Clinical Research Director of the Seattle Cancer Care Alliance. Nelson led the study on behalf of the PCF International Prostate Cancer Dream Team.

Breaks in DNA occur thousands of times in each cell cycle, and normal cells have about half a dozen ways to combat DNA damage. However, cells with mutated DDR genes have deficient repair pathways, leading to the accumulation of mutations that can promote tumor formation.

Most notable of these are defects in BRCA1/2 genes, which are infamous for increasing a woman's risk of breast and ovarian cancer. In the study, Nelson and colleagues found that BRCA2 specifically represented 44% of all identified mutations, making it the most common heritable mutation in men with advanced prostate cancer.

Prostate cancer patients with DDR mutations may benefit from targeted treatment with a relatively new class of drugs known as PARP inhibitors.


 

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