Dominika Wokołorczyk1, Wojciech Kluźniak1, Klaudia Stempa1, Bogna Rusak1, Tomasz Huzarski1,2, Jacek Gronwald1, Katarzyna Gliniewicz1, Aniruddh Kashyap1, Sylwia Morawska1, Tadeusz Dębniak1, Anna Jakubowska1,3, Marek Szwiec4, Paweł Domagała5, Jan Lubiński1, Steven A Narod6,7, Mohammad R Akbari6,7, Cezary Cybulski8. 1. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland. 2. Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland. 3. Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland. 4. Clinics of Oncology, University Hospital in Zielona Góra, Zielona Góra, Poland. 5. Department of Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland. 6. Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada. 7. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. 8. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland. cezarycy@pum.edu.pl.
Abstract
BACKGROUND: The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers. METHODS: We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers. RESULTS: A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006). CONCLUSION: In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.
BACKGROUND: The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers. METHODS: We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers. RESULTS: A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006). CONCLUSION: In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.
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