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DATA ANALYSIS OF 179 BRCA1 OR BRCA2 MUTATED FAMILIES. THE ITALIAN CONSORTIUM FOR HEREDITARY BREAST AND OVARIAN CANCER.

DATA ANALYSIS OF 179 BRCA1 OR BRCA2 MUTATED FAMILIES. THE ITALIAN CONSORTIUM FOR HEREDITARY BREAST AND OVARIAN CANCER. DATABASES Italian Consortium for Hereditary breast and ovarian cancer. Aviano. Milano. Padova. Chieti - Aquila. Modena. Pisa. 179 families BRCA mutated.

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DATA ANALYSIS OF 179 BRCA1 OR BRCA2 MUTATED FAMILIES. THE ITALIAN CONSORTIUM FOR HEREDITARY BREAST AND OVARIAN CANCER.

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  1. DATA ANALYSIS OF 179 BRCA1 OR BRCA2 MUTATED FAMILIES. THE ITALIAN CONSORTIUM FOR HEREDITARY BREAST AND OVARIAN CANCER.

  2. DATABASESItalian Consortium for Hereditary breast and ovarian cancer Aviano Milano Padova Chieti-Aquila Modena Pisa 179 families BRCA mutated 104 families BRCA1 mutated 75 families BRCA2 mutated

  3. Other Tumors Breast 1:1 1:2 1:3 1:4 2:1 2:2 2:3 Colonrectum 50 CNS 50 ~60 ~60 51 3:1 3:2 3:3 3:4 3:5 3:6 3:7 BRCA2 Q2960X Breast 31 Breast 48 Breast 44 BRCA2 BRCA2 68 Breast sx 40 34 52 47 Breast 30 Breast 65 67 75 73 4:1 4:2 4:3 4:4 4:5 4:6 4:7 4:8 4:9 4:10 WT WT BRCA2 50 47 WT 47 42 39 40 38 34 Breast 37 44 48 5:1 5:2 5:3 22 17 18

  4. BRCA1 AND BRCA2 RECURRENT MUTATIONS

  5. BRCA mutated family profile HBC 83 (46 %) HBOC 69 (39 %) HOC 11 ( 6 %) MBC 16 (9 %) Total 179 Families Hereditary Breast Cancer (HBC, with cases of female breast cancer only) , Hereditary Breast and Ovarian Cancer (HBOC, with cases of both breast and ovarian cancer), Hereditary Ovarian Cancer (HOC, with cases of ovarian cancer only) and Male Breast Cancer (MBC, with at least 1 case of male breast cancer).

  6. BRCA1 BRCA2 TOT P HBC 41 42 83 0.04 HBOC 52 17 69 0.0004 HOC 10 1 11 0.03 MBC 1 15 13 0.00003 TOT104 75 179 Statistically significant differences were observed between two genes within family groups

  7. ANALYSIS OF AGE AT ONSET OF BREAST AND OVARIAN CANCER IN MUTATION CARRIERS BRCA1 BRCA2 Average age of BrCa onset 40.4±10.6 45.5±10.9 on mutation carriers Average age of OvCa onset 48.3±8.9 57.8±7.2 on mutation carriers P<0.005 (Kruskal-Wallys Test)

  8. KAPLAN-MEIER ESTIMATE OF PROPORTION OF DISEASE-FREE MUTATION CARRIERS BRCA2 N=89 (12 censored) BRCA1 N=133 (17 censored) Age P < 0.005, Cox-Mantel log-rank test

  9. HETEROGENEITY BETWEEN LOCI FOR CANCERS OTHER THAN BREAST OR OVARIAN

  10. We summarized all our results about heterogeneity between loci by fitting a logistic regression model to the following variables: 1)the age of cancer onset in the proband 2)presence of ovarian cancer in the family (either in the proband or in a relative) 3)presence of male breast cancer in the family (either in the proband or in a relative) 4)presence of either prostate or pancreas cancer in the family. All four variables were statistically associated with the mutated locus at the 0.001 significance level, and were weakly correlated one to the other

  11. 0.8-0.9 FREQUENCY OF OBSERVED BRCA MUTATIONS AS A FUNCTION OF P (THE PROBABILITY OF FINDING A BRCA2 MUTATION) BRCA1 BRCA2

  12. CONCLUSIONS • A relevant proportion of mutations occur in multiple independent families across Italy • A substantial level of phenotypic heterogeneity exists between BRCA1- and BRCA2-mutated families • A regressive model based on this heterogeneity is highly efficient in directing the mutational screening These are a critical step in the development of simple and less expensive diagnostic approaches to DNA analysis and facilitate carriers detection and genetic counseling

  13. *Partecipant Units: Co-ordinating unit: Generoso Bevilacqua, M. Adelaide Caligo, Giovanna Cipollini, Paolo Aretini, Elisa Sensi, Chiara Ghimenti, Mariella Tancredi. Dipartimento di Oncologia, dei Trapianti e delle NuoveTecnologie in Medicina. Divisione di Anatomia Patologica e di Diagnostica Molecolare ed Ultrastrutturale, Università di Pisa. Silvano Presciuttini Dipartimento di Biomedicina Sperimentale Infettiva e Pubblica, Università di Pisa. Alessandra Viel, Manuela Santarosa, Dolcetti Riccardo, Centro Riferimento Oncologico, IRCCS, Aviano, Maria Grazia Tibiletti, Universita' dell'Insubria, Varese. Unit1: Renato Mariani-Costantini, Alessandro Cama, Mario Falchetti: Dipartimento di Oncologia e Neuroscienze, Università "G. D'Annunzio", Chieti ;Cristina D'Amico, Laura Ottini: Dipartimento di Medicina Sperimentale, Università "La Sapienza", Roma. Paolo Marchetti, Enrico Ricevuto, Z. Cristiana di Rocco, Roberta Bisegna, Corrado Ficorella. Dipartimento di Medicina Sperimentale, Università dell'Aquila. Unit2: Luigi Chieco-Bianchi, Emma D’Andrea, Arcangela De Nicolo, Simona Agata, Dipartimento di Sc. Oncologiche e Chirurgiche, Sezione di Oncologia, Università di Padova. Chiara Menin, Marco Montagna, IST - Sezione Biotecnologie, Università di Padova. Unit3: Paolo Radice, Barbara Pasini, Valeria Pensotti, Rosella Crucianelli, Alberto Conti, Giovanbattista Spatti, Giuseppe De Palo, Marco Pierotti. Istituto Nazionale Tumori, Milano. Unit4: Sergio Ferrari, Laura Cortesi, Daniela Turchetti, Chiara Bertoni, Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena.

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