Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort

• Published in: Journal of hematology and oncology Vol. 14; no. 1; pp. 18 - 4
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London BioMed Central 18.01.2021; BioMed Central Ltd; BMC
• Subjects: Analysis; BRCA1 protein; BRCA1/2; BRCA2 protein; Breast cancer; Cancer; Cancer Research; Carcinoma; Care and treatment; Classification; Cohort; Exons; Family medical history; Genetic aspects; Genomes; Genomics; Health aspects; Hematology; Hospitals; Innovations; Invasiveness; Laboratories; Letter to the Editor; Medicine; Medicine & Public Health; Minority & ethnic groups; Mutation; Oncology; Otolaryngology; Patients; Population; Reclassification; Risk assessment; Science; Surgery; VUS; Beijing China; China; Macao; Breast cancer; Cohort; VUS; Reclassification; BRCA1/2
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-01010-0

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.