16% of the familial BC cases [2]. Other BC sus-ceptibility genes include TP53 [16], PTEN [15], ATM [24],LKB1/STK11 [8], CHEK2 [28], BRIP1/FANCJ [27], andPALB2/FANCN [22]. However to date, the majority offamilial BC cases can not be attributed to mutations in oneof the known susceptibility genes.The discovery of the breast cancer susceptibility geneBRCA2asthegenedefectiveintheFanconianemia(FA)-D1complementation group [11], the identification of BRIP1(BRCA1 InteractingProtein)[3, 12,13] andPALB2 (PartnerAnd Localizer of BRCA2) [23, 32] as the genes responsiblefor the FA-J and FA-N complementation groups, respec-tively, established a clear link between breast cancer sus-ceptibility and FA. Fanconi anemia (FA) is a recessivelyinherited chromosomal instability syndrome with autosomalor X-linked mode of inheritance, and is characterized by anincreased susceptibility to several forms of malignancies [1,17].Thediseaseiscausedbymutationsinoneofthe13genesso far identified [18]. The FA gene products interact in acommon pathway whereby most of the proteins (FANCA, -B, -C, -E, -F, -G, -L, and -M) form a multiprotein complexthat is required for the monoubiquitination of FANCD2 andFANCI.However,thismodificationstepisnotinfluencedbyFANCD1(BRCA2),FANCJ(BRIP1),orFANCN(PALB2),and hence these proteins seem to act downstream of thisprocess. FANCD2 and FANCI are thought to form a proteincomplex (ID complex), which translocates to DNA damagesites where it co-localizes with the downstream FA proteins,BRCA2/FANCD1, BRIP1/FANCJ, and PALB2/FANCNand other proteins that are involved in the recognition andrepair of DNA damage, such as BRCA1, ATM, NBS, andRAD51 [31].Several studies explored whether heterozygous femalecarriers for a mutation in one of the FA genes are atincreased risk for breast cancer. To date, only mutations inthe ‘‘downstream’’ FA genes have been found to signifi-cantly elevate the risk of developing breast cancer. Het-erozygous mutations in BRIP1/FANCJ and PALB2/FANCNappear to increase the risk 2- and 2.3-fold, respectively [22,27]. Risk assessment has been based on screening fortruncating mutations in these genes in familial breastcancer (FBC) patients lacking mutations in BRCA1/2.Furthermore, FANCD2 mutations, have been suggested toplay a role in the development of breast cancer based onobservations of Fancd2 knockout mice, which demon-strated a high incidence of epithelial tumors, includingmammary and ovarian tumors [10]. However, in humans asignificant contribution of FANCD2 mutations to FBCcould not be established [14, 26].