BRCA1 and BRCA2 associations

[cmungall]

This is not strictly in the domain of Mondo but Mondo is where most people see this - e.g. when browsing for genes associated with breast cancer on the monarch site

OMIM has an entry

https://omim.org/entry/114480 BREAST CANCER (alt title: BREAST CANCER, FAMILIAL)

with a lot of associated genes

note the table on OMIM includes BRCA2 but not BRCA1

In the HPOA file we have BRCA1 as Mendelian and BRCA2 as polygenic

NCBIGene:672 BRCA1 MENDELIAN OMIM:114480 ftp://ftp.ncbi.nlm.nih.gov/gene/DATA/mim2gene_medgen NCBIGene:675 BRCA2 POLYGENIC OMIM:114480 ftp://ftp.ncbi.nlm.nih.gov/gene/DATA/mim2gene_medgen

I realize that applying the MENDELIAN/POLYGENIC distinction to cancer subsceptibility is inherently fraught and perhaps a line is somewhat arbitrary, but it seems conventional to treat BRCA1 and BRCA2 together, even if the risk profiles are different, e.g

https://www.ncbi.nlm.nih.gov/books/NBK1247/

[cmungall]

Some more publications on Mendelian vs Polygenic/Complex:

Mendelian Inheritance:

• BRCA2 mutations follow a Mendelian inheritance pattern, where a single inherited mutation significantly increases the risk of breast cancer. Studies have shown that BRCA2 mutations account for a substantial proportion of hereditary breast cancer cases (Ford et al., 1998).
• Individuals with BRCA2 mutations have a markedly increased risk of developing breast cancer, with penetrance estimates indicating that a high percentage of mutation carriers develop the disease by age 70 (Struewing et al., 1997).

Polygenic Model:

• Polygenic model where multiple low-penetrance genes contribute to breast cancer susceptibility. This model posits that BRCA1 and BRCA2 mutations alone cannot account for all familial breast cancer cases, implying the involvement of other genetic factors. (Antoniou et al., 2001).
• Studies incorporating polygenic risk scores (PRS) have demonstrated that common genetic variants can modify cancer risks even for BRCA1/2 mutation carriers. This indicates that the cancer risk is influenced by multiple genetic factors, supporting the polygenic model (Lecarpentier et al., 2017).