BRCA1 and BRCA2 variants appear to be associated with more than just breast, ovarian, prostate, and pancreatic cancers, according to research published in JAMA Oncology.

Results of a large-scale, registry-based study suggest that pathogenic variants in BRCA1/2 are also associated with an increased risk of biliary tract, gastric, and esophageal cancers.

To identify cancer types and clinical characteristics associated with pathogenic variants in BRCA1 and BRCA2, researchers conducted a study of patients with 14 common cancer types and a control group of population-matched individuals.  

Continue Reading

The researchers analyzed data on 63,828 patients with biliary tract, breast, cervical, colorectal, endometrial, esophageal, gastric, liver, lung, lymphoma, ovarian, pancreatic, prostate, and kidney cancers. The data were derived from BioBank Japan, a multi-institutional, hospital-based registry containing DNA and clinical information from across Japan.

The control cohort included 37,086 adults age 20 years and older with no history or family history of cancer. 

The researchers found that pathogenic variants in BRCA1 were associated with biliary tract cancer (odds ratio [OR], 17.4), and pathogenic variants in BRCA2 were associated with esophageal cancer (OR, 5.6). Variants in BRCA1 (OR, 5.2) and BRCA2 (OR, 4.7) were associated with gastric cancer.

Overall, pathogenic variants in BRCA1 were significantly associated with an increased risk of ovarian, female breast, biliary tract, gastric, and pancreatic cancers. Pathogenic variants in BRCA2 were significantly associated with an increased risk of female and male breast, ovarian, prostate, pancreatic, gastric, and esophageal cancers.

“The results of this large-scale, registry-based, case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of 7 cancer types,” the researchers wrote. “These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Momozawa Y, Sasai R, Usui Y, et al. Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants. JAMA Oncol. Published online April 14, 2022. doi:10.1001/jamaoncol.2022.0476