Multicenter retrospective study of cancer risks associated with germline BARD1 pathogenic/likely pathogenic variants

Autosomal dominantly inherited pathogenic variants in BARD1 (BRCA1-associated RING domain 1) are known to predispose females to a moderately increased lifetime risk of breast cancer. A multicenter retrospective study estimated the relative and absolute risks of ovarian, prostate, male and female breast, pancreatic, biliary tract, and colorectal cancers associated with germline BARD1 pathogenic and likely pathogenic variants (PVs/LPVs). The authors performed a secondary retrospective analysis of data comprising 445 three-generation pedigrees with confirmed BARD1 PVs/LPVs from 25 institutions in the US. The risks were estimated using a Bayesian survival model that incorporated information from the SEER Program. The analysis confirmed the previously established increased risk of female breast cancer (relative risk 3.53; 95% CI 1.95-5.81) and found positive associations with female pancreatic cancer (3.76; 2.16-7.25), male pancreatic cancer (2.89; 1.66-5.61) and prostate cancer (3.02; 1.95-4.71). The predictive absolute risks to age 85 years were 41.84% (95% CI 23.09-68.91) for female breast cancer, 4.80% (2.76-9.25) for female pancreatic cancer, 3.98 (2.29-7.73) for male pancreatic cancer, and 36.11% (23.29-56.29) for prostate cancer. There was no evidence of association for biliary tract cancer or male colorectal cancer. The authors conclude that these results support BARD1’s association with female breast cancer and suggest associations with pancreatic and prostate cancers.