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Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort
Liu, Yun1,2,3; Wang, Honglian4; Wang, Xin5; Liu, Jiaqi5; Li, Junjian1; Wang, Xiang5; Zhang, Yun6,7; Bai, Zhigang6,7; Zhou, Qinghua8; Wu, Ying8; Shen, Yi8; Weng, Xiaoling2,3; Liu, Fatao9; Guo, Jiancheng10; Di, Lijun11; Gires, Olivier12; Zhang, Zhongtao6; Chen, Yiding13,14; Wang, Hongxia1
2021-12-01
Source PublicationJournal of Hematology and Oncology
ISSN1756-8722
Volume14Issue:1
Abstract

Accurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls. Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers. Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2–5 and 15–23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.

KeywordBrca1/2 Breast Cancer Cohort Reclassification Vus
DOI10.1186/s13045-020-01010-0
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology ; Hematology
WOS SubjectOncology ; Hematology
WOS IDWOS:000608735900001
Scopus ID2-s2.0-85100011504
Fulltext Access
Citation statistics
Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorZhang, Zhongtao; Chen, Yiding; Wang, Hongxia
Affiliation1.State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 100 Haining Road, China
2.State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3.Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
4.AITA Biomedical Research Institute, Shanghai, China
5.Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
6.Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 95 Yong’an Road, China
7.Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing, China
8.Department of Surgery, Luwan Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
9.Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China
10.Center for Precision Medicine, Zhengzhou University School of Medicine, Zhengzhou, China
11.Cancer Center, Faculty of Health Science, University of Macau, Macao
12.Department of Otorhinolaryngology, Grosshadern Medical Center, Ludwig Maximilians University of Munich, Munich, Germany
13.Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 88 Jiefang Road, China
14.The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, China
Recommended Citation
GB/T 7714
Liu, Yun,Wang, Honglian,Wang, Xin,et al. Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort[J]. Journal of Hematology and Oncology,2021,14(1).
APA Liu, Yun,Wang, Honglian,Wang, Xin,Liu, Jiaqi,Li, Junjian,Wang, Xiang,Zhang, Yun,Bai, Zhigang,Zhou, Qinghua,Wu, Ying,Shen, Yi,Weng, Xiaoling,Liu, Fatao,Guo, Jiancheng,Di, Lijun,Gires, Olivier,Zhang, Zhongtao,Chen, Yiding,&Wang, Hongxia.(2021).Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort.Journal of Hematology and Oncology,14(1).
MLA Liu, Yun,et al."Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort".Journal of Hematology and Oncology 14.1(2021).
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