Ultraconserved elements (UCEs) are segments of >200 bp length showing absolute 
sequence identity between orthologous regions of human, rat and mouse genomes. 
The selection factors acting on these UCEs are still unknown. Recent studies 
have shown that UCEs function as long-range enhancers of flanking genes or are 
involved in splicing when overlapping with exons. The depletion of UCEs among 
copy number variation as well as the significant under-representation of 
single-nucleotide polymorphisms (SNPs) within UCEs have also revealed their 
evolutional and functional importance indicating their potential impact on 
disease, such as cancer. In the present study, we investigated the influence of 
six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed 
an association with familial breast cancer risk. Whereas rs9572903 showed only a 
borderline significant association, the frequency of the rare [G] allele of 
rs2056116 was higher in cases than in controls indicating an increased familial 
breast cancer risk ([G] versus [A]: odds ratio (OR) = 1.18, 95% confidence 
interval (CI) 1.06-1.30, P = 0.0020; [GG] versus [AA]: OR = 1.41, 95% CI 
1.15-1.74, P = 0.0011). Interestingly, comparing with the older age group, the 
ORs were increased in woman younger than 50 years of age ([G] versus [A]: OR = 
1.27, 95% CI 1.11-1.45, P = 0.0005; [GG] versus [AA]: OR = 1.60, 95% CI 
1.22-2.10, P = 0.0007) pointing to an age- or hormone-related effect. This is 
the first study indicating that SNPs in UCEs might be associated with cancer 
risk.