BRCA mutation in Chinese population: Preliminary results from the The Hong Kong hereditary and High-Risk Breast Cancer Programme (HRBC programme).

22063 Background: Inherited mutations in the cancer susceptibility genes BRCA1/2 accounts for about 70-90% of familial breast cancer based on Caucasian data. However, 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 versus Caucasians. The Hong Kong Hereditary and High Risk Breast Cancer Programme ( www.BreastCancerFamily.org ) was established in March 2007. This is first of its kind in Hong Kong and provides clinical testing, genetic counseling and research in Chinese population. The data from this programme will be entered in The Hong Kong Hereditary Breast Cancer Family Registry ( www.asiabreastregistry.com ).,Probands diagnosed to have breast cancer age <50, a family/personal history of breast and/or ovarian cancer, bilateral breast cancer, male breast cancer, and triple negative carcinoma were recruited. Genetic counseling was given and consent for testing were obtained. Blood and tumor samples were collected and processed for DNA and RNA extraction. The entire coding regions and flanking introns of BRCA1 and 2 were screened for germline mutations using full gene sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). RNA analysis were done on suspicious VUS.,69 Chinese Probands' blood have been sequenced and analysed. 19 (28%) deleterious mutations were identified of which 3 (16%) were novel mutations. 9 (47%) were BRCA 1 mutations and 10 (53%) were BRCA 2 mutations. 66.6% had first degree relatives with breast cancer. 8 families of probands have also been tested: a total of 26 family members, 17 of these have BRCA mutations and only 9 of them have breast cancers. 4 male family members had BRCA mutations but no breast cancer.,Approximately 30% of the tested blood samples from clinically high risk Chinese probands carry a deleterious mutation. A high yield of BRCA mutations and a higher rate of BRCA2 mutations were found in our population. Further research on the spectrum of the mutations in Chinese will allow the tailor-making of an ethnic-based risk assessment model and preventative measures to be taken. No significant financial relationships to disclose.