BRCA1 and BRCA2 Germline Mutations in Japanese with Hereditary Breast Cancer Families.

We examined germline mutations in BRCA1 and BRCA2 in 23 Japanese breast cancer families, using PCR-SSCP analysis. The same nonsense mutation (exon 5, Leu63ter) of BRCA1 was detected in two defferent families. Three different mutations resulting in a truncated BRCA2 protein (exon 9, 20, 24) were detected in three different families, including one male case of breast cancer. One base substitution mutation in BRCA2, A10462G, was detected in the other two families. Although the mean age of onset for breast cancer in families with the BRCA1-mutation was 50 years, the age of onset in families with the BRCA2-mutation was from 28 to 43 years. Among the 23 families examined, two families had members with ovarian cancers, three had members with prostate cancers, and one had a pancreatic cancer. However, none of these families was positive for the BRCA1 orBRCA2 mutation. Histopathologically, we observed a prevalence of histological grade 3 in BRCA1/2-associated familial breast cancers, because of nuclear atypia, structural atypia and mitotic activity. It is suggested that BRCA2 may play a more important role than BRCA1 in Japanese familial breast cancers, and these mutations are related to the aggressive nature and highly proliferative activity of the tumors.