Missing ethnic information in current BRCA variant databases
Zixin Qin, San Ming Wang
To the Editor,
BRCA mutation substantially increases risk of breast and ovarian cancer. Extensive efforts have identified large quantities of human BRCA1 andBRCA2 (BRCA ) variants, and the data have been developed into multiple BRCA variant reference databases to guide clinical applications worldwide. Human BRCA genes are rapidly evolving (Huttley et al, 2000; Lou et al, 2014). This is reflected by the highly ethnic-specific nature of human BRCA variation (Rebbeck et al, 2018; Kwong et al, 2016; Bhaskaran et al, 2019). For example,BRCA variation in Africans is substantially different from non-Africans that nearly 90% of BRCA variants in Africans were not present in non-Africans (Figure 1) (Shen et al, 2000; John et al, 2007; Churpek et al, 2015; Zheng et al, 2018; Fiebel et al, 2019). Ethnic-specificBRCA variation is important for understanding the evolution of human BRCA , genetic basis of BRCA variation and cancer, and for using ethnic-based variation information for precise diagnosis, prevention and treatment of BRCA related cancer in diversified ethnic populations.
To understand current knowledge of ethnic-specific BRCAvariation, we analyzed the ethnic information in the major BRCAdatabases including BRCA Exchange, ClinVar, ENIGMA, LOVD, BIC, BRCA-share and ARUP. The results show that except BIC, the current BRCA databases basically do not provide ethnic information for their collected BRCA variants (Figure 1B). The reason for lack of ethnic information in current BRCA databases can be that submitters do not provide the ethnic information as considered it unnecessary. This needs to be changed by the increased evidence in ethnic-specific BRCA variation and its relevant in cancer application. Another reason can be that ethnic origin is classified as private information being protected by law, therefore, both submitters and database curators don’t want to include ethnic information. However, the BRCA data in public BRCAdatabases are all anonymous such that ethnic information is not relevant to privacy issue.
We believe that the ethnic information needs to be included in current BRCA variant databases to benefit clinical applications.