Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of women from Shanghai, China.Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer.The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively.Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent.
IntroductionAlthough the incidence of breast cancer in China is about one-third that in the United States (1), the overall rate of breast cancer in women from China has been increasing (2). Little is known regarding the role of inherited susceptibility genes in breast cancer risk among Chinese women. To develop genetic screening guidelines for both Chinese women and United States women of Chinese descent, a population-based assessment of BRCA1 and BRCA2 germ-line mutation distribution and frequency is needed.To date, information regarding the frequency of BRCA1 and BRCA2 mutations in Chinese women with breast cancer has been derived from two small hospital-based reports. In the first, 76 consecutive breast cancer cases diagnosed before age 40, and 16 women with a family history of breast or ovarian cancer, were screened for germ-line mutations in BRCA1 (3). Protein truncating mutations were observed in 8.6% of women. In the second study, 3.8% of 130 tumors collected from mastectomy patients in Hong Kong were found to carry protein-truncating mutations in BRCA1 (4). The prevalence was 8.0% in patients diagnosed under age 45 (4). In the same study, investigators observed a single variant, 589delCT, in three unrelated patients from within a single province of Southern China, suggesting a possible founder effect. However a later more detailed study of 60 early onset breast cancer cases did not reveal any additional carriers (4, 5). Neither study examined the role of BRCA2 mutations in Chinese women.Studies of women...
