Genetic factor affecting prostate cancer prognosis identified

Hereditary mutations in the BRCA2 gene predispose patients to a worse evolution of prostate cancer and a greater risk of developing metastasis. Their survival rates are worse than those of the rest of the patients with the disease.

"Whilst the majority of patients with prostate cancer have an excellent prognosis, one of the biggest challenges we face in daily clinical practice is the difficulty of identifying those patients in which the illness can be fatal," said study coauthor David Olmos, MD, Head of the Prostate Cancer and Genitourinary Tumours Clinical Research Unit at the Spanish National Cancer Research Centre (CNIO).

To search for genetic markers that offer clues as to the evolution of the illness, the investigators examined 61 patients with prostate cancer who were also carriers of mutations in the BRCA2 gene, which is a gene that suppresses tumors and protects DNA; 18 patients with mutations in BRCA1, a gene whose function is similar to BRCA2; and 1,940 patients who had neither mutation.

The magnitude of the study makes it one of the largest studies carried out so far in prostate cancer patients carrying BRCA1 or BRCA2 mutations; these genes are traditionally known for being responsible for familial breast and ovarian cancer syndrome.

Patient analyses showed that BRCA1 and BRCA2 gene mutation carriers were at greater risk for having more advanced prostate cancer at the time of diagnosis, as well as of developing metastasis. This study was published in Journal of Clinical Oncology (2013; doi:10.1200/JCO.2012.43.1882).

Furthermore, within the subgroup of patients in which the disease had not spread at the time of diagnosis, 23% of the carriers of mutations in these genes developed metastasis over the following 5 years, compared to 7% of those patients who were not carriers. Five years after diagnosis, 19% of BRCA2 mutation carriers with early-stage disease had died, compared with 4% of the noncarriers; there were no significant differences between BRCA1 mutation carriers and noncarriers.

"These data turn the BRCA2 gene into the first genetic factor for prostate cancer prognosis," said first author Elena Castro, MD, also of CNIO. She added, "The results of this study suggest the need for a paradigm shift in the clinical management of patients with prostate cancer who are carriers of mutations in the BRCA genes; current treatment standards for these patients appear to be insufficient and there are no specific action guidelines."

"Now that we have managed to identify patients with potentially lethal disease, our next challenge is to explore the most adequate treatments with the least side effects that have a real impact on survival," said Olmos.

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