Several components of the Fanconi anaemia (FA) family of proteins allow the formation of the DNA repair complex foci formed by proteins such as BRCA1/2 and RAD51. Because
the genes that participate in the DNA repair pathway have been described as low-penetrance breast cancer susceptibility
genes, we postulated that variants in FA genes could also be associated with sporadic breast cancer risk. We studied seven SNPs in FANCA, FANCL and FANCD2 in a total of 897 consecutive and non-related sporadic breast
cancer cases and 1033 unaffected controls from the Spanish population. We observed a statistically significant association
with sporadic breast cancer for the variant
rs2272125 (L1366L) located on FANCD2 (OR per allele ¼ 1.35; 95% C.I. 1.09–1.67; P ¼ 0.005). Both haplotype and diplotype analyses confirmed this association, where
one haplotype and pooled diplotypes carrying it were associated with more than 4-fold risk (P ¼ 0.007 and P ¼ 0.006,
respectively). Screening for potential causal variants in FANCD2 was performed, detecting one in the putative promoter region, which is located in a phylogenetically conserved motif with consensus binding sites for some
transcriptional factors, suggesting a functional implication.
Our data indicate that a relationship between FANCD2 and poradic breast cancer risk may exist.This study was supported by the grant BFI2003-03852. EB and LPF were
funded by the Comunidad Auto´noma de Madrid and by the Spanish Ministry of
Science and Technology (MCT), respectively. We would like to thank A ´ lvaro
Ruibal (University Hospital, Santiago de Compostela), and Santiago Palacios
(Instituto Palacios, Madrid) for the use of samples of cases and controls. We
would also like to thank Raquel Rodrı´guez-Lo´pez for her contribution to the
beginning of this work, and Fa´tima Mercadillo, Alicia Barroso, Emilio
Gonza´lez, Jesu´s Lo´pez, Victoria Ferna´ndez and Rocı´o Leto´n for their expert
technical skills
