Jacopo Azzollini1, Giulietta Scuvera2, Eleonora Bruno3, Patrizia Pasanisi4, Daniela Zaffaroni5, Mariarosaria Calvello6, Barbara Pasini7, Carla B Ripamonti8, Mara Colombo9, Valeria Pensotti10, Paolo Radice11, Bernard Peissel12, Siranoush Manoukian13. 1. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Jacopo.Azzollini@istitutotumori.mi.it. 2. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: giulietta.scuvera@hotmail.it. 3. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Biomedical Sciences for Health, University of Milan, Italy. Electronic address: Eleonora.Bruno@istitutotumori.mi.it. 4. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Patrizia.Pasanisi@istitutotumori.mi.it. 5. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Daniela.Zaffaroni@istitutotumori.mi.it. 6. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: mariarosaria.calvello@yahoo.it. 7. Department of Medical Sciences, University of Turin, Italy; Department of Predictive Medicine and Prevention, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: barbara.pasini@unito.it. 8. Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Carla2.Ripamonti@istitutotumori.mi.it. 9. Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Mara.Colombo@istitutotumori.mi.it. 10. IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy; Cogentech Cancer Genetics Test Laboratory, Milan, Italy. Electronic address: valeria.pensotti@ifom.eu. 11. Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: paolo.radice@istitutotumori.mi.it. 12. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Bernard.Peissel@istitutotumori.mi.it. 13. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: Siranoush.Manoukian@istitutotumori.mi.it.
Abstract
BACKGROUND: BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. METHODS: BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95% CI were estimated to test the relative effectiveness of each criterion. RESULTS: The overall DR was 29.3%. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8%-80.0%) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9% and 7.2%, respectively). CONCLUSIONS: The observed estimates, albeit confirming a DR above 10% for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.
BACKGROUND:BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. METHODS:BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95% CI were estimated to test the relative effectiveness of each criterion. RESULTS: The overall DR was 29.3%. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8%-80.0%) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9% and 7.2%, respectively). CONCLUSIONS: The observed estimates, albeit confirming a DR above 10% for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.
Authors: Carla B Ripamonti; Paolo Bossi; Siranoush Manoukian; Laura Locati; Mara Colombo; Maria L Carcangiu; Andrea Vingiani; Lisa Licitra; Paolo Radice Journal: Virchows Arch Date: 2021-06-08 Impact factor: 4.064
Authors: J Maksimenko; A Irmejs; G Trofimovičs; D Bērziņa; E Skuja; G Purkalne; E Miklaševičs; J Gardovskis Journal: Hered Cancer Clin Pract Date: 2018-06-05 Impact factor: 2.857
Authors: Laura Caleca; Mara Colombo; Thomas van Overeem Hansen; Conxi Lázaro; Siranoush Manoukian; Michael T Parsons; Amanda B Spurdle; Paolo Radice Journal: Cancers (Basel) Date: 2019-01-28 Impact factor: 6.639
Authors: Mengjia Shen; Libo Yang; Ting Lei; Lin Xiao; Li Li; Peichuan Zhang; Weiyi Feng; Feng Ye; Hong Bu Journal: Transl Cancer Res Date: 2019-04 Impact factor: 1.241