Prostate cancer progression and survival in BRCA2 mutation carriers
Laufey Tryggvadóttir1, Linda Vidarsdóttir, Tryggvi Thorgeirsson
1Icelandic Cancer Registry, PO Box 5420, Iceland. laufeyt@krabb.is
Journal of the National Cancer Institute
|June 15, 2007
Summary
The Icelandic BRCA2 999del5 founder mutation is linked to a higher risk of aggressive prostate cancer. Carriers of this mutation experienced earlier diagnosis, more advanced tumors, and significantly shorter survival times.
Area of Science:
- Genetics and Oncology
- Cancer Genomics
- Prostate Cancer Research
Background:
- BRCA2 gene mutations increase prostate cancer risk.
- The association between BRCA2 mutations and prostate cancer progression remains unclear.
Purpose of the Study:
- To investigate the impact of the Icelandic BRCA2 999del5 founder mutation on prostate cancer progression.
- To compare prostate cancer-specific survival, disease stage, and tumor grade in mutation carriers versus non-carriers.
Main Methods:
- Population-based study of Icelandic prostate cancer patients (1955-2004).
- BRCA2 mutation status determined for 527 patients.
- Stage and grade analysis on 89 matched patients (carriers and non-carriers).
- Multivariable regression models used to estimate hazard ratios for survival.
Main Results:
- 5.7% of patients carried the BRCA2 999del5 mutation.
- Carriers diagnosed younger (69.0 vs 74.0 years), with more advanced stage (79.3% vs 38.6%) and higher grade (84.0% vs 52.7%).
- Carriers had significantly shorter median survival (2.1 vs 12.4 years) and increased risk of prostate cancer death (HR=3.42).
Conclusions:
- The Icelandic BRCA2 999del5 founder mutation is strongly associated with rapidly progressing, lethal prostate cancer.
- This mutation is a significant predictor of poor prognosis in prostate cancer patients.
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