Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation.
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.
Aretini
Paolo
P
Section of Oncogenetics, Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa, Pisa, Italy. p.aretini@med.unipi.it
D'Andrea
Emma
E
Pasini
Barbara
B
Viel
Alessandra
A
Mariani Costantini
Renato
R
Cortesi
Laura
L
Ricevuto
Enrico
E
Agata
Simona
S
Bisegna
Roberta
R
Boiocchi
Mauro
M
Caligo
Maria Adelaide
MA
Chieco-Bianchi
Luigi
L
Cipollini
Giovanna
G
Crucianelli
Rosella
R
D'Amico
Cristina
C
Federico
Massimo
M
Ghimenti
Chiara
C
De Giacomi
Clelia
C
De Nicolo
Arcangela
A
Della Puppa
Lara
L
Ferrari
Sergio
S
Ficorella
Corrado
C
Iandolo
Davide
D
Manoukian
Siranoush
S
Marchetti
Paolo
P
Marroni
Fabio
F
Menin
Chiara
C
Montagna
Marco
M
Ottini
Laura
L
Pensotti
Valeria
V
Pierotti
Marco
M
Radice
Paolo
P
Santarosa
Manuela
M
Silingardi
Vittorio
V
Turchetti
Daniela
D
Bevilacqua
Generoso
G
Presciuttini
Silvano
S
D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012044:Regression Analysis; D012307:Risk Factors