title: Comparison between CaGene 5.1 and 6.0 for BRCA1/2 mutation prediction: a retrospective study of 150 BRCA1/2 genetic tests in 517 families with breast/ovarian cancer.
abstract: During the past years, several empirical and statistical models have been developed to discriminate between carriers and non-carriers of germline BRCA1/BRCA2 (breast cancer 1, early onset/breast cancer 2, early onset) mutations in families with hereditary breast or ovarian cancer. Among these, the BRCAPRO or CaGene model is commonly used during genetic counseling, and plays a central role in the identification of potential carriers of BRCA1/2 mutations. We compared performance and clinical applicability of BRCAPRO version 5.1 vs version 6.0 in order to assess diagnostic accuracy of updated version. The study was carried out on 517 pedigrees of patients with familial history of breast or ovarian cancer, 150 of which were submitted to BRCA1/2 mutation screening, according to BRCAPRO evaluation or to criteria based on familial history. In our study, CaGene 5.1 was more sensitive than CaGene 6.0, although the latter showed a higher specificity. Both BRCAPRO versions better discriminate BRCA1 than BRCA2 mutations. This study evidenced similar performances in the two BRCAPRO versions even if the CaGene 6.0 has underestimated the genetic risk prediction in some BRCA mutation-positive families. Genetic counselors should recognize this limitation and during genetic counseling would be advisable to use a set of criteria in order to improve mutation carrier prediction.
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Health and Territorial Sciences (DISPUTer), School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti-Pescara, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Antonucci
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Health and Territorial Sciences (DISPUTer), School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti-Pescara, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Provenzano
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Health and Territorial Sciences (DISPUTer), School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti-Pescara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sorino
authors.affiliation: Psychometric Laboratory, DISPUTer, School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti-Pescara, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Balsamo
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti, Italy.|Aging Research Center, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Gitana Maria
authors.initials: GM
authors.lastname: Aceto
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti, Italy.|Aging Research Center, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Battista
authors.affiliation: Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences 'G. d'Annunzio' University, Chieti-Pescara, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Cianchetti
authors.affiliation: Laboratory of Pharmacology, DISPUTer, School of Medicine and Health Sciences, G. d'Annunzio University Chieti-Pescara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ballerini
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Palka
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Health and Territorial Sciences (DISPUTer), School of Medicine and Health Sciences, 'G. d'Annunzio' University, Chieti-Pescara, Italy.|Aging Research Center, 'G. d'Annunzio' University, Chieti, Italy.
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005817:Genetic Counseling; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human