title: Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer.
abstract: We determined the prevalence and characteristics of BRCA1/2 germline mutations in a large cohort of Chinese women with breast cancer. A total of 5931 unselected Chinese women with breast cancer were enrolled in this study and underwent testing for BRCA1/2 mutations. Of these, 543 patients were familial breast cancer, 1033 were early-onset disease (≤40 years) without family history of breast cancer, and 4355 were sporadic breast cancer. In total, 232 patients (3.9 %) carried a BRCA1 or BRCA2 mutation (110 in BRCA1and 122 in BRCA2) in this cohort of 5931 patients. BRCA1/2 mutation rate was 16.9 % (92/543) in familial breast cancers, 5.2 % (54/1033) in early-onset breast cancers (≤40 years), and 2.0 % in sporadic breast cancers (>40 years), respectively. The BRCA1/2 mutation rate was 27.0 % in 111 familial breast cancers diagnosed at and before the age of 40. 41.4 % of mutations in this cohort were specific for Chinese population. Recurrent mutations accounted for 44.8 % of the entire mutations in 2382 cases that BRCA1 and BRCA2 genes were fully sequenced in this study. Both BRCA1 and BRCA2 mutation carriers were significantly more likely to be early-onset and bilateral breast cancers, high-grade cancer, and to have a family history of breast cancer compared with non-carriers. BRCA1 mutation carriers were more likely to be triple-negative cancer than BRCA2 mutation carriers and non-carriers. Our data provide guidelines for Chinese women with breast cancer who should undergo BRCA1/2 genetic testing; additionally, recurrent mutations account for nearly half of the mutations and some of them are specific for Chinese women.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Jiuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Tie
authors.initials: T
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.
authors.forename: Benyao
authors.initials: B
authors.lastname: Lin
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China. zlxyt2@bjmu.edu.cn.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1/2 mutation; Breast cancer; Chinese women; Prevalence