Abstract
Background: Mutations in the BRCA2 gene are associated with an increased risk of prostate cancer, but it is not known whether they are associated with progression of the disease. We compared prostate cancer-specific survival, disease stage, and tumor grade between prostate cancer patients carrying the Icelandic BRCA2 999del5 founder mutation and noncarriers. Methods: Using population-based registries, we identified all 596 prostate cancer patients who were diagnosed in Iceland during 1955 through 2004 among 29603 male relatives of unselected breast cancer probands. BRCA2 mutation status could be determined for 527 patients (88.4%). Stage and grade were abstracted from original records, blindly with respect to mutation status, for a subgroup of 89 patients that included all mutation carriers and, for each carrier, two control patients without the BRCA2 999del5 mutation who were matched to the carrier on years of diagnosis and birth. Hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer-specific survival were estimated using multivariable regression models. All statistical tests were two-sided. Results: The mutation was carried by 30 patients (5.7%). Compared with noncarriers, BRCA2 999del5 mutation carriers had a lower mean age at diagnosis (69.0 years versus 74.0 years; P = .002), more advanced tumor stage (stages 3 or 4, 79.3% versus 38.6%; P<.001), higher tumor grade (grades G3-4, 84.0% versus 52.7%, P = .007), and shorter median survival time (2.1 years, 95% CI = 1.4 to 3.6 years, versus 12.4 years, 95% CI = 9.9 to 19.7 years). Carrying the BRCA2 999del5 mutation was also associated with an increased risk of dying from prostate cancer (adjusting for year of diagnosis and birth, HR = 3.42, 95% CI = 2.12 to 5.51); the association remained after adjustment for stage and grade (HR = 2.35, 95% CI = 1.08 to 5.11). The prognosis of BRCA2 999del5 mutation carriers was not associated with period of diagnosis or with relatedness to breast cancer probands. Conclusions: The Icelandic BRCA2 999del5 founder mutation was strongly associated with rapidly progressing lethal prostate cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 929-935 |
| Number of pages | 7 |
| Journal | Journal of the National Cancer Institute |
| Volume | 99 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 20 Jun 2007 |
Bibliographical note
Funding Information:We thank the Department of Pathology at Landspitali University Hospital, the Department of Pathology at the Regional Hospital – University Hospital Akureyri, and the Histopathology Laboratory, Alfheimar 74, Reykjavik, as well as the Biobank of the Icelandic Cancer Society for providing tissue samples. We also thank chief technician at the University Hospital Department of Pathology, Kristrún Ólafsdóttir, for her work with the paraffin-embedded tissue samples. In addition, we thank the Icelandic Centre for Research, the Icelandic Cancer Society, and the Margret Bjorgulfsdottir Memorial Fund for financing this research. Last but not least, we are indebted to the patients diagnosed with prostate cancer who participated in this study. The sponsors had no role in the study design, the collection of the data, the analyses, the interpretation of the findings, the preparation of the manuscript, or the decision to submit the manuscript for publication.