Two potential breast cancer susceptibility genes, encoding the BRCA1-interacting proteins ZNF350 (or ZBRK1) and BRIP1 (or BACH1), have been identified in yeast two-hybrid screens.
Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles.
Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.
BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer.
Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.
We used a SNP tagging approach to evaluate the association between common variants (minor allele frequency>or=0.05) in BRIP1 and the risks of breast cancer and invasive ovarian cancer.
Most of these genes, such as BRCA1, BRCA2, TP53, CHEK2, ATM, and FANCJ/BRIP1, function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer.
Fanconi anaemia (FA) has recently become an attractive model to study breast cancer susceptibility (BRCA) genes, as three FA genes, FANCD1, FANCN and FANCJ, are identical to the BRCA genes BRCA2, PALB2 and BRIP1.
Identification in 2002 of the Fanconi anaemia (FA) gene FANCD1 as BRCA2 and recent studies indicating that heterozygous mutations in FANCN/PALB2 and FANCJ/ BRIP1 predispose to breast cancer have emphasised an important connection between the FA and BRCA pathway.
Given the growing evidence now linking BRCA1, BRCA2, and the FA pathway, as well as the involvement of FA proteins (BRCA2/FANCD1 and PALB2/FANCN) in breast cancer susceptibility, we sought to evaluate the contribution of FANCJ gene alterations regarding breast cancer susceptibility among our cohort of 96 breast cancer individuals from high-risk non-BRCA1/2 French Canadian families.