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Title: Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer.
Austin Authors: Nguyen-Dumont, Tú;Dowty, James G;MacInnis, Robert J;Steen, Jason A;Riaz, Moeen;Dugué, Pierre-Antoine;Renault, Anne-Laure;Hammet, Fleur;Mahmoodi, Maryam;Theys, Derrick;Tsimiklis, Helen;Severi, Gianluca;Bolton, Damien M ;Lacaze, Paul;Sebra, Robert;Schadt, Eric;McNeil, John;Giles, Graham G;Milne, Roger L;Southey, Melissa C
Affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
CESP Inserm U1018, Faculté de Médecine-Univ. Paris-Sud, Faculté de Médecine-UVSQ, Université Paris-Saclay, 94805 Villejuif, France
Gustave Roussy, 94805 Villejuif, France
Surgery (University of Melbourne)
CESP Inserm U1018, Faculté de Médecine-Univ. Paris-Sud, Faculté de Médecine-UVSQ, Université Paris-Saclay, 94805 Villejuif, France
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC 3168, Australia
Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC 3010, Australia
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
Issue Date: 24-Mar-2021 2021-03-24
Publication information: Cancers 2021; 13(7): 1495
Abstract: While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7-12.4)), BRCA1 (5.5 (1.8-16.6)), and ATM (3.8 (1.6-9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.
DOI: 10.3390/cancers13071495
ORCID: 0000-0002-6217-0182
PubMed URL: 33804961
ISSN: 2072-6694
Type: Journal Article
Subjects: aggressive prostate cancer
gene panel testing
genetic risk factors
Appears in Collections:Journal articles

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