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 can help to determine which patients are likely to develop a progressive or lethal disease and would therefore benefit from early treatment. The BRCA2 gene on chromosome 13 has been associated with familial male and female breast cancer. A founder mutation in this gene has been detected 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 prostate cancer patients related to BRCA2 positive breast cancer probands and to estimate the prevalence of this mutation in unselected prostate cancer patients. To examine the potential role of this mutation in prostate cancer we analyzed prostate cancer cases from 16 BRCA2 families and all available samples from individuals diagnosed with prostate cancer in Iceland over a period of 1 year. The risk ratio of prostate cancer 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 probands. Of 26 prostate cancer cases found in these families 12 were analyzed, and 8 of these (66.7%) had the BRCA2 mutation. All of these patients 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 poor prognosis.
Sigurdsson
S
S
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.
Thorlacius
S
S
Tomasson
J
J
Tryggvadottir
L
L
Benediktsdottir
K
K
Eyfjörd
J E
JE
Jonsson
E
E
D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics; D018567:Breast Neoplasms, Male / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007055:Iceland; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D017384:Sequence Deletion; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors