Nat Commun: Study on the risk of breast cancer in BRCA1/BRCA2 mutation carriers

Breast cancer (BC) is the most common cancer among women worldwide, and family history of BC is one of the most important risk factors for the disease.
Women with a history of BC among first-degree relatives have a two-fold higher risk of BC than women without a family history.

Previous studies have shown that rare mutations in the BRCA1 or BRCA2 genes can explain about 15-20% of the onset of familial BC.
A recent prospective cohort study showed that the 80-year cumulative risk of BC for BRCA1 mutation carriers was 72%, and that for BRCA2 mutation carriers was 69%.

Flow chart of sample selection for cases

Therefore, the risk of breast cancer (BC) in BRCA1/BRCA2 mutation carriers varies according to the patient's genetic and family history.
About 50 common mutants have been found to be associated with the risk of BC.
However, there are currently no mutants that are particularly associated with the risk of BC.

Known BC susceptibility SNP analysis process

In this study, the researchers conducted a case-only genome-wide association study, aiming to compare the frequency of related genotypes in 60,212 general BC populations and 13,007 cases carrying BRCA1 or BRCA2 mutations.
Researchers have identified five new association sites, two of which are related to BRCA1 mutation carriers, and the other three are related to BRCA2 mutation carriers, and these association sites have nothing to do with the risk of disease in the general population.
The rs60882887 locus on chromosome 11p11.
2 is one of these locus, and the MADD, SP11 and EIF1 genes that were previously predicted as potential targets of BC are nearby.

All in all, the results of this study will help develop polygenic risk scores for BC patients with BRCA1 and BRCA2 mutations.