Cancer Risks Associated With Germline BARD1 Pathogenic/Likely Pathogenic Variants: A Multicenter Study of 445 Families

BARD1

Heterozygous germline pathogenic or likely pathogenic BARD1 variants

Cancer risks associated with germline pathogenic and likely pathogenic BARD1 variants had not previously been estimated from a genotype-first perspective. The authors performed a secondary retrospective analysis of 445 three-generation pedigrees from 25 institutions, using a Bayesian survival model incorporating data from the SEER Program. The study confirms the increased risk of female breast cancer (RR 3.53) and identifies associations with female (RR 3.76) and male (RR 2.89) pancreatic cancer, as well as with prostate cancer (RR 3.02). Absolute risks to age 85 are estimated at 41.84% for female breast cancer, 4.80% and 3.98% for female and male pancreatic cancer, and 36.11% for prostate cancer. No association was found for biliary tract cancer or male colorectal cancer, and the signals for male breast, ovarian and female colorectal cancers warrant cautious interpretation.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Families recruited through clinical centres remain exposed to selection bias, and confidence intervals are wide for pancreatic cancer. The prostate signal, with an absolute risk of 36.11% to age 85, needs replication before guiding surveillance of male carriers. BARD1 is already captured by exome and genome sequencing: the task now is to translate these estimates into genetic counselling for relatives of both sexes.

Analysis by Dr Thibaut Benquey