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 t wo site-specific breast cancer families, the same mutation was detecte d; a nonsense mutation at codon 63 encoding a truncated small protein. It was demonstrated that the mutant allele cosegregated with breast c ancer patients within a family and was absent in healthy Japanese, sug gesting a breast cancer-predisposing allele. The average age at diagno sis was 44 and 55 years in each family with BRCA1 mutation. No bilater al breast cancer patients were present in the BRCA1 mutation-positive families, although five were present in the BRCA1-negative families. N o 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. T hus, the proportion of families who inherit the mutated BRCA1 allele s eems to be small among Japanese breast cancer families and Japanese br east-ovarian cancer families.