Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants

BRCA1 and BRCA2 were identified in the 1990s as the causative genes underlying hereditary

breast and ovarian cancer syndrome with genetic testing beginning during the same decade for
treatment of patients and their relatives. The target BRCA1 and BRCA 2 cancer types have
expanded to include prostate and pancreatic cancers. Risk for additional cancer types, such as
biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer
and stomach cancer has been reported by analyzing family members for the presence of
pathogenic variants and performing case-control analyses. To date, the evidence has not been
considered sufficient to be adopted into clinical management guidelines.

DNA samples and clinical information from 63,828 patients with 14 common cancer types and
37,086 controls were sourced from a multi-institutional hospital-based registry in Japan
between 2003 and 2018.

The results of this study suggest that pathogenic variants in BRCA1 and BRCA 2 were associated
with the risk of 7 cancer types. Biliary tract, esophageal, and gastric cancer were significantly
associated with BRCA1 and/or BRCA2 in addition to the 4 established cancer types. Six other
cancer types showed an association.

This information can improve genetic testing of BRCA1 and BRCA2 for various cancer types for
Asian countries and encourages similar research in other countries.
Jama Oncology doi:10.1001/jamaoncol.2022.0476