Background and significance of constructing a Chinese population-specific BRCA variant reference database

Breast cancer is one of the most common cancers and a leading cause of cancer-related death among women worldwide. In China, more than 260,000 new breast cancer cases and nearly 70,000 breast cancer-related deaths are reported each year. Therefore, developing effective strategies for the early prevention and diagnosis of breast cancer is of great importance for controlling the occurrence of breast cancer in the Chinese population.

Approximately 10%–20% of breast cancer cases are caused by hereditary mutations occurring in functionally important genes, among which BRCA1 and BRCA2 are the most representative susceptibility genes. BRCA1 and BRCA2 play critical roles in maintaining genomic stability. Severe functional mutations in these two genes can lead to genomic instability, thereby significantly increasing the risk of breast cancer and other types of cancer in mutation carriers.

To date, thousands of BRCA gene mutations have been identified, many of which have been classified as pathogenic variants. Several BRCA mutation reference databases established based on these variant data have been widely used in the prevention, diagnosis, and treatment of cancers associated with BRCA mutations.

Recent studies have shown that BRCA mutations exhibit strong ethnic specificity. Existing BRCA mutation data are primarily derived from Caucasian populations in Europe and North America. Relying solely on these data as a universal reference is insufficient for accurately identifying BRCA mutation carriers in non-Caucasian populations, which may result in missed diagnoses or misdiagnoses. Therefore, it is necessary to establish ethnicity-specific BRCA mutation reference databases to enable more precise identification of mutation carriers with similar ethnic backgrounds.

China has the largest population in the world. Among the over 1.4 billion people in China, it is estimated that there are between 1 and 2 million BRCA mutation carriers, although the exact number remains unclear. Previous studies have demonstrated that BRCA mutations in the Chinese population differ significantly from those observed in other ethnic populations.

Through large-scale data mining, standardization, annotation, and clinical impact classification, we established this Chinese population-specific reference database of BRCA1 and BRCA2 variants.

We hope that the establishment and open access of this database will facilitate research and clinical applications related to BRCA-associated cancers in the Chinese population, and promote both domestic and international collaboration in this field.