Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer

Manuela Santarosa, Alessandra Viel, Riccardo Dolcetti, Diana Crivellari, Maria Donatella Magri, Maria Antonietta Pizzichetta, Maria Grazia Tibiletti, Angelo Gallo, Salvatore Tumolo, Laura Del Tin, Mauro Boiocchi

Research output: Contribution to journalArticlepeer-review


Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCAI and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCAI mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron I was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCAI mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCAI in families with only breast cancers was 9%. In the 46 Italian families studied, BRCAI mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCAI genetic testing mainly when ovarian cancer is present.

Original languageEnglish
Pages (from-to)581-586
Number of pages6
JournalInternational Journal of Cancer
Issue number5
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


Dive into the research topics of 'Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer'. Together they form a unique fingerprint.

Cite this