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First genetic factor in prostate cancer prognosis identified

09.04.2013
CNIO researchers, together with scientists in the United Kingdom, have revealed that hereditary mutations in the BRCA2 gene predispose patients to a worse evolution of the illness and a greater risk of developing metastasis

Patients with prostate cancer and hereditary mutations in the BRCA2 gene have a worse prognosis and lower survival rates than do the rest of the patients with the disease.

This is the main conclusion to come out of a study published this week in the Journal of Clinical Oncology, in which David Olmos, Head of the Prostate Cancer and Genitourinary Tumours Clinical Research Unit at the Spanish National Cancer Research Centre (CNIO), has taken part in, along with Elena Castro, a member of the Unit, and British researchers at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

According to Olmos: "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".

In order to search for genetic markers that offer clues as to the evolution of the illness, the study's authors examined 61 patients with prostate cancer who were also carriers of mutations in the BRCA2 gene (a gene that suppresses tumours and that protects DNA), 18 patients with mutations in BRCA1 (a gene whose function is similar to BRCA2) and 1,940 patients in which the presence of mutations in both genes had been excluded.

THE LARGEST STUDY TO DATE

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.

Furthermore, within the subgroup of patients in which the disease had not spread at the time of diagnosis, 23% of carriers of mutations in these genes developed metastasis over the following five 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 non-carriers; there were no significant differences between BRCA1 mutation carriers and non-carriers.

Castro, the first author of the article, says: "These data turn the BRCA2 gene into the first genetic factor for prostate cancer prognosis", to which she adds: "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", says Olmos.

Prostate cancer is the second most common type of cancer in men worldwide, although in developed countries it is the most frequently found tumour.

This is the case in Spain, where more than 25,000 new cases are diagnosed each year, making it the third cause of cancer-related deaths in men.

Over the past few decades, an increase in cases has been observed due, above all, to longer life expectancies and the widespread use of the PSA (Prostate-Specific Antigen) screening test in the general population. Fortunately, a decrease in mortality for this disease has also been observed, due to the majority of diagnoses being carried out at an early stage and due to improved treatments.

Even so, there are still cases in which the disease is fatal and efforts as well as resources are being dedicated to identifying those patients with the worst prognosis and to establishing the most appropriate therapeutic strategies.

CNIO'S PROSTATE CANCER & GENITOURINARY TUMOURS CLINICAL RESEARCH UNIT

The Unit was created in September 2012 in order to improve the quality of life and survival rates of prostate cancer patients. Via a multidisciplinary approach, in which molecular biologists, bioinformatics engineers and clinical oncologists work together, the Unit aims to accelerate the translation of new knowledge generated by CNIO and the international scientific community into clinical practice.

The creation of this new Unit has been made possible thanks to the support received from the Spanish Association Against Cancer (AECC) and the CRIS Foundation Against Cancer.

CNIO'S CLINICAL FAMILIAL CANCER UNIT

The Clinical Familial Cancer Unit (UCCF) offers genetic counselling to patients and their relatives suspected of having a hereditary form of cancer. It carries out the identification, evaluation and study of families in which a mutation in susceptible genes might exist, such as in the case of the BRCA1 and BRCA2 genes. The UCCF Consultancy is located within the Medical Oncology Service at the Hospital Universitario de Fuenlabrada (HUF), and works closely with oncologists, other HUF service professionals and other CNIO Groups and Units, in order to evaluate and provide clinical surveillance to patients at risk of suffering from familial, hereditary forms of cancer. The UCCF also offers its services to healthcare professionals and hospitals anywhere in the country.

Nuria Noriega | EurekAlert!
Further information:
http://www.cnio.es

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