Germline mutation of BRCA1 in Japanese breast cancer families.

We analyzed germline mutations of the BRCA1 gene in 18 Japanese breast cancer families and two Japanese breast-ovarian cancer families. In two site-specific breast cancer families, the same mutation was detected; a nonsense mutation at codon 63 encoding a truncated small protein. It was demonstrated that the mutant allele cosegregated with breast cancer patients within a family and was absent in healthy Japanese, suggesting a breast cancer-predisposing allele. The average age at diagnosis was 44 and 55 years in each family with BRCA1 mutation. No bilateral breast cancer patients were present in the BRCA1 mutation-positive families, although five were present in the BRCA1-negative families. No germline mutations of BRCA1 were detected in the two breast-ovarian cancer families examined in this study, although BRCA1 mutation plays a major role in breast-ovarian cancer families in Western countries. Thus, the proportion of families who inherit the mutated BRCA1 allele seems to be small among Japanese breast cancer families and Japanese breast-ovarian cancer families.