BRCA mutation in Chinese population: results from the Hong Kong hereditary and high risk breast cancer programme (HRBCP) and the Hong Kong hereditary and high risk breast cancer family registry.

Abstract

BACKGROUND: Little is known about the frequency and spectrum of BRCA 1/2 mutations among Chinese population. Previous research suggests possible differences in the prevalence and penetrance of inherited mutations in these genes among Asians and the earlier presentation of breast cancer in Asian population may have more relevance to genetic causes. The access to genetic counseling and testing in Asia have been limited. The HRBCP (www.HRBCP.org) was established in 2007. This is first in Hong Kong and provides genetic testing, counseling and research on the spectrum of the disease in Asia and in particular Chinese population. The data from this programme will be entered in the newly established The Hong Kong Hereditary Breast Cancer Family Registry. METHODS: Probands who were diagnosed to have breast cancer age 50 or below, have a family history or personal history of breast and/or ovarian cancer, bilateral breast cancer, male breast cancer, triple negative breast carcinoma were recruited. Genetic counseling were given and consent for testing were obtained. Blood and tumor samples were collected. The entire coding regions of the extracted DNA/RNA and flanking introns of BRCA1 and 2 were screened for germline mutations using full gene sequencing and MLPA. RESULTS: A total of 119 Chinese have been sequenced and analysed. 21 (18%) deleterious mutations were identified of which 4 were novel mutations. 8 (38%) were BRCA 1 mutations and 13 (62%) were BRCA 2 mutations. 66.6% had first degree relatives with breast cancer. 49 (41.2%) were under the age of 40 years old of which 11 (22%) were found to carry a BRCA mutation. 7 (64%) of this younger age group with mutation have family history of breast cancer. For the other 4, 1 had triple negative cancer, 1 had a family history of ovarian cancer, 1 unknown and 1 with no risk except for young age. Of the 37 family members tested, 21 (57%) have BRCA mutations and only 9 of them have breast or ovarian cancers. 1 only had stomach cancer. 6 male family members were found to carry the BRCA mutation with no history of cancer. CONCLUSIONS: Approximately 18% of the tested blood samples from clinically high risk Chinese women carry a deleterious mutation in BRCA1 or 2. In contrast to Caucasian data, there was a comparative higher rate of BRCA2 mutations. Further research on the spectrum of the mutations in Chinese and other Asian population will allow the tailor-making of an ethnic-based risk assessment model and also screening, prophylactic and preventative measures to be taken.