BRCA2 MUTATION IN ICELANDIC PROSTATE-CANCER PATIENTS

Molecular genetic analysis of prostate cancer has gained considerable attention in recent years. The hope is to find genetic markers that ca n help to determine which patients are likely to develop a progressive or lethal disease and would therefore benefit from early treatment. T he BRCA2 gene on chromosome 13 has been associated with familial male and female breast cancer. A founder mutation in this gent? has been de tected in the Icelandic population. This is a 5-bp deletion that leads to an early termination and truncated protein. Clustering of prostate cancers in some of the Icelandic BRCA2 families implies that mutation carriers are at increased risk of developing cancer of the prostate. The aim of the study was to investigate this mutation in Icelandic pro state cancer patients related to BRCA2 positive breast cancer probands and to estimate the prevalence of this mutation in unselected prostat e cancer patients. To examine the potential role of this mutation in p rostate cancer we analyzed prostate cancer cases from 16 BRCA2 familie s and all available samples from individuals diagnosed with prostate c ancer in Iceland over a period of 1 year. The risk ratio of prostate c ancer was 4.6 (1.9-8.8) in first-degree relatives and 2.5 (1.2-4.6) in second-degree relatives of the 16 BRCA2 positive breast cancer proban ds. Of 26 prostate cancer cases found in these families 12 were analyz ed, and 8 of these (66.7%) had the BRCA2 mutation. All of these patien ts developed an advanced disease, and all have died of prostate cancer (median survival 22.5 months). Among unselected cases 3.1% (2/65) had the mutation and developed an advanced disease as well. This specific mutation in the BRCA2 gene is found in a subset of Icelandic prostate cancer cases and appears to be a marker for pear prognosis.