- A global resource that contains information on thousands of inherited variants in the BRCA1 and BRCA2 genes is now publicly available, which will help facilitate risk scoring and accelerate innovative cancer research, according to the National Institutes of Health (NIH).
Available through a website and new smartphone app, the resource allows clinicians and researchers to review expert classifications of variants in these major cancer predisposition genes. These reviews will play a role clinicians’ individual assessments of questions related to cancer prevention, screening, and intervention for high-risk patients.
The BRCA Exchange was created through the BRCA Challenge, a five-year demonstration project designed to increase sharing of BRCA1 and BRCA2 data. The BRCA Challenge was funded in part by NIH’s National Cancer Institute (NCI), and through the Cancer Moonshot.
Certain inherited variants in BRCA1 and BRCA2 genes can increase the risk of breast, ovarian, and other cancers by varying degrees, while others are not associated with disease.
NIH notes that it is essential for both clinicians and patients to know whether a given variant is associated with disease, and the likelihood that these disease-associated variants will cause cancer. However, until now, the available data on inherited variants in these genes was not collected in a comprehensive, complete way.
The BRCA Exchange dataset is made up of information from existing clinical databases, including the Breast Cancer Information Core, ClinVar, and the Leiden Open Variation Database, as well as population databases and data from clinicians, laboratories, and clinicians around the world.
Currently, more than 20,000 unique BRCA1 and BRCA2 variants are included in the database. Of those variants, more than 6100 have been classified by an expert panel, the Evidence-based Network for the Interpretation of Germline Mutant Alleles.
Approximately 3700 of these classified variants are known to cause disease.
The resource is also a demonstration project, showing that comprehensive data sharing is possible for other cancer predisposition genes, as well as for genes associated with other diseases.
By collecting data from data resources all over the world, the BRCA Exchange database could result in the inclusion of rare variants that are infrequently observed.
“This project has yielded a meta-analysis of BRCA1 and BRCA2 variants collected from multiple sources to understand how experts annotate specific mutations in the two genes,” said Stephen J. Chanock, MD, director of NCI’s Division of Cancer Epidemiology and Genetics and lead author of the paper.
“There’s an urgent need for sharing data in cancer predisposition research. The BRCA Exchange is proof of principle that large-scale collaboration and data sharing can be achieved and can provide the latest and best quality information to enable clinicians and individuals to improve care.”
The project’s next steps will include collaborating with other global data generators and data holders, further technical improvement, and increased engagement with patients and patient advocates around the world.