Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort
Open Access
- 18 January 2021
- journal article
- letter
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 14 (1), 1-4
- https://doi.org/10.1186/s13045-020-01010-0
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.Keywords
Funding Information
- National Natural Science Foundation of China (81772802, 82073269)
- Shanghai science and technology innovation action plan of China (17JC1404400, 16DZ19102)
- Special Funds for Technological Innovation of Shanghai Jiao Tong University (YG2016MS22)
- National Science and Technology Major Project (2019ZX09301-158)
- Chinese Academy of Science (XDA12020223)
- Natural Science Foundation of Zhejiang Province (LZ16H160002)
- Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
- National Science and Technology Major Project (2019ZX09301-158)
This publication has 4 references indexed in Scilit:
- Germline variation in BRCA1/2 is highly ethnic‐specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patientsInternational Journal of Cancer, 2019
- Accurate classification of BRCA1 variants with saturation genome editingNature, 2018
- Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer PatientsClinical Cancer Research, 2017
- The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) studyBreast Cancer Research and Treatment, 2015