Abstract

The purpose of this investigation is to study the frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Mutation analysis of BRCA1 and BRCA2 by SSCP was conducted on the 113 breast cancer patients (probands) with at least 1 breast cancer (site-specific breast cancer families, n = 101) or 1 ovarian cancer (breast/ovarian cancer families, n = 12) patient in their first-degree relatives. Fifteen deleterious mutations (13.3%), including 8 nonsense and 7 frameshift mutations, were identified in BRCA1, and 21 deleterious mutations (18.6%), including 8 nonsense, 12 frameshift and 1 splice-site mutations, were identified in BRCA2. In site-specific breast cancer families, mutation frequency of BRCA1 or BRCA2 was high in families with 3 or more breast cancer patients (36%, 9/25), early onset (40 < or = years old) breast cancer patients (38%, 19/50) or bilateral breast cancer patients (40%, 6/15). In breast/ovarian cancer families, mutations of BRCA1 (58.3%, n = 7), but not BRCA2 (0%, n = 0), were observed. BRCA1 codon 63 (TTA to TAA) nonsense mutation and BRCA2 frameshift mutation (5802 del AATT) were observed in 4 and 7 independent families, respectively. Haplotype analysis has suggested that carriers of each of these mutations have common ancestors. These results demonstrate that family profiles are important determinants of risk for carrying a BRCA1 or BRCA2 mutation and that cumulative frequency of BRCA1 and BRCA2 mutations in Japanese breast cancer families (31.9%) is within the range observed in Caucasian breast cancer families. Presence of Japanese founder mutations has also been suggested.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.