Damaging missense variants in innate immunity genes are associated with earlier age of breast cancer onset in BRCA1 185delAG carriers

Damaging missense variants in innate immunity genes associated with earlier breast cancer onset

This whole-exome sequencing study examined 322 Israeli women carrying the BRCA1 185delAG founder variant to identify genetic modifiers of breast cancer penetrance. Carrying potentially damaging missense variants in innate immunity genes was associated with earlier breast cancer onset, with a hazard ratio of 3.62 for the “natural killer cell activation” gene set. These results suggest a role for innate immunity pathways as modifiers of BRCA1 penetrance, beyond classic polygenic scores.

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

An interesting but very preliminary mechanistic lead: a limited sample size, a single founder variant and a gene-set approach call for independent replication before any clinical use. The idea that innate immune modifiers, not just polygenic score, shape breast cancer onset age in BRCA1 carriers is appealing for individualized risk prediction. At this stage, with no direct impact on practice.