BRCA1 and BRCA2 Mutations in Women from Shanghai China

Abstract

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...

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women

“…Of those interviewed, 470 (85%) women with fibrocystic conditions and 323 (86%) women with breast cancer provided a blood sample. Additionally, women with breast cancer diagnosed from November 1989 to September 1995 were selected from a study of BRCA1 and BRCA2 mutations, which was designed to retrospectively recruit diagnosed cases of breast cancer under age 45, along with an equal number of older cases (Suter et al [56]). Retrospective recruitment was possible because in the BSE cohort, the average probability of survival from breast cancer for six years after diagnosis was greater than 80% (Thomas et al [52]).…”

“…Genomic DNA was isolated from buffy coat using a salt-precipitation (Miller et al [58]) or a phenol-chloroform method (Suter et al [56];Bell et al [59];Maniatis et al [60]), or from whole blood (red cell solution) using the QIAamp® DNA Blood Midi Kit (Qiagen, Alameda, CA). DNA concentration was determined by UV spectrophotometry.…”

BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

“…However, our current understanding of BRCA1 mutations and their contribution to sporadic early-onset breast cancer (<35 years old) has arisen primarily from studies conducted in Caucasian women. To date, the little knowledge we have of BRCA1 germline mutations in Chinese women with early-onset breast cancer is mainly derived from Shanghai and Hong Kong (Tang et al, 1999;Suter et al, 2004). However, information on BRCA1 mutations in Uighur women with sporadic early-onset breast cancer is largely lacking.…”

“…This is consistent with rates in other Asian ethnic groups (Hall et al, 2009). Another study, by Suter et al (2004) found that the rates of BRCA1 mutations in sporadic breast cancers were 0.7% (4/590) in Shanghai of China. Moreover, in early-onset breast cancer, mutation rates of these genes were 5.1% in east regions of China (Li et al, 2008).…”

Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment

“…Although the entire incidence of breast cancer is lower in Chinese women as compared with Caucasian women, early-onset breast cancer is, however, more common in Chinese women than Caucasian, and approximately 20% of breast cancer patients are diagnosed before the age of 40 years in Chinese women compared with 10% in Caucasian women 1) . In addition, approximately 10% of breast cancer patients have a family history of breast cancer in Chinese women 2) .…”