Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation

• Published in: Breast cancer research and treatment Vol. 81; no. 1; pp. 71 - 79
• Main Authors: ARETINI, Paolo, D'ANDREA, Emma, CALIGO, Maria Adelaide, CHIECO-BIANCHI, Luigi, CIPOLLINI, Giovanna, CRUCIANELLI, Rosella, D'AMICO, Cristina, FEDERICO, Massimo, GHIMENTI, Chiara, DE GIACOMI, Clelia, DE NICOLO, Arcangela, DELLA PUPPA, Lara, PASINI, Barbara, FERRARI, Sergio, FICORELLA, Corrado, IANDOLO, Davide, MANOUKIAN, Siranoush, MARCHETTI, Paolo, MARRONI, Fabio, MENIN, Chiara, MONTAGNA, Marco, OTTINI, Laura, PENSOTTI, Valeria, VIEL, Alessandra, PIEROTTI, Marco, RADICE, Paolo, SANTAROSA, Manuela, SILINGARDI, Vittorio, TURCHETTI, Daniela, BEVILACQUA, Generoso, PRESCIUTTINI, Silvano, MARIANI COSTANTINI, Renato, CORTESI, Laura, RICEVUTO, Enrico, AGATA, Simona, BISEGNA, Roberta, BOIOCCHI, Mauro
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.09.2003; Springer Nature B.V
• Subjects: Analysis; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Cancer research; Cancer therapies; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Genes; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Humans; Italy; Male; Mammary gland diseases; Medical sciences; Mutation; Ovarian cancer; Pedigree; Phenotype; Regression Analysis; Risk Factors; Tumors; Italy; Europe; pedigree analysis; BRCA1; BRCA2; allelic heterogeneity; Epidemiology; Genital diseases; Heterogeneity; Ovary; expressivity; Predisposition; Familial cancer; hereditary breast/ovarian cancer; Mammary gland; Tumor suppressor gene; Human; Family study; Malignant tumor; Gene expression; Female genital diseases; Mammary gland diseases; Ovarian diseases; Allele; Germ line; Risk factor; Mutation
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1023/A:1025428807472

Mutations in BRCA1 and BRCA2 show different expressivity with respect to cancer risk, and allelic heterogeneity may be present in both genes. We collected 179 pedigrees with identified germline mutation (104 BRCA1 and 75 BRCA2), ascertained in six collaborating centers of the Italian Consortium for Hereditary Breast and Ovarian Cancer. Significant heterogeneity was detected for several variables, and a logistic regression model including age of diagnosis in the proband, presence of ovarian cancer in the family, presence of prostate or pancreatic cancer in the family, and presence of male breast cancer in the family proved to be effective in predicting the presence of a mutation in a gene rather than the other. Excess of familial aggregation of both breast and ovarian cancer was observed in both genes. Proportion of ovarian cancer was increased in the 5' portion of BRCA1, and presence of prostate or pancreatic cancer in a family was correlated with presence of ovarian cancer in BRCA2.