inherited mutations in DNA repair genes may predispose to prostate cancer metastatic

inherited mutations in DNA repair genes may predispose to prostate cancer metastatic -

inherited mutations in the genes that work to repair DNA may contribute to cancer metastatic prostate most recognized previously, according to a study today in the New England Journal of Medicine. Although uncommon in the general population, the heritable mutations in specific types of gene repair of DNA, such as BRCA1 and BRCA2, are known to predispose to prostate cancer. However, the rate of these mutations in men with metastatic prostate cancer previously unknown.

This revolutionary study found that more than 10 percent of men with aggressive prostate cancer that has spread outside the prostate have inherited mutations in DNA repair genes - more than four times the rate of the general population and more than twice the rate of men with localized prostate cancer. Men with such mutations could benefit from a targeted treatment already approved for patients with ovarian cancer with these mutations, such as PARP inhibitors or platinum drugs.

Dr. Peter Nelson, a member of human biology, clinical research and public health sciences divisions at Fred Hutchinson Cancer Research Center and lead author and correspondent of the study commented: "The result is surprising and important for men with prostate cancer this information can prioritize certain therapies. It is also important for the family members as they may have inherited a gene that predisposes them to develop the one of several types of cancer and increased awareness could improve early detection and treatment. These results present a compelling argument for updating guidelines on prostate cancer include germline DNA testing as a part of standard treatment for men with metastatic prostate cancer. "Dr. Nelson is also a professor of medical oncology at the University of Washington School of Medicine and an oncologist specializing in therapies for cancer early prostate and advanced, pathology and genome sciences at Seattle Cancer Care Alliance.

the main results of the study revealed that 11.8 percent of men with metastatic prostate cancer, regardless of age or family history of prostate cancer, deleterious germline mutations in one of the 20 DNA repair genes studied. Men with prostate cancer metastatic were five times more likely to have these inherited mutations in DNA repair genes as the general population. In particular, men with advanced prostate cancer had a risk 18 times higher a carrier of a BRCA2 mutation than men without prostate cancer.

Dr. Colin C. Pritchard, Associate Professor of Laboratory Medicine Department, and deputy director of the Genetics and Tumor Laboratory solid at Washington University School of Medicine is the first author of the study . "We were delighted to learn how high the percentage of inherited mutations of DNA repair gene in men with metastatic prostate cancer because the potential benefits of genetic testing. We already know a lot about some DNA repair genes such as BRCA2, but for others, we are just beginning to understand how germline mutations contribute to the risk and selection of optimal treatment of prostate cancer. Since these men are considering test themselves, it is important to note that all DNA repair genes are the same, and clinical genetic testing requires specialists to ensure proper guidance, accurate detection of mutation, and the results are correctly interpreted and communicated . "

project pooled the results of 692 men with metastatic prostate cancer included in seven case series in several institutions, including Fred Hutch and the University of Washington through the support of StandUp2Cancer and prostate cancer Foundation. Each site conducted the independent detection of mutations in DNA repair genes 20 using next generation sequencing tests.

As mutations in certain DNA repair genes predispose to other types of cancer, including breast, ovary and pancreas, the family members of cancer patients metastases prostate with inherited mutations may be offered genetic testing, counseling and enrollment in research studies, if any.

Dr. Heather H. Cheng, assistant professor of medical oncology at the University of Washington and deputy member of the Clinical Research Division at Fred Hutchinson Cancer Research Center is also co-author of the study, and leads a new clinical genetics of prostate cancer at SCCA to advise men with prostate cancer on genetic testing and how the results can help to adapt their treatment options.

An important strength of these results is that the men included in the study were not chosen because of their family history of prostate cancer or age, and different genetic tests have produced the same percentage of men who have inherited mutations.