It is always a big challenge to interpret the mechanisms of action of risk-associated SNPs from GWAS analysis, given that more and more SNPs are found to lie in non-coding regions of the genome. Most recently, researchers have identified two novel lncRNAs that were transcribed in the proximal cancer risk loci and characterized the important roles in tumorigenesis (Figure 3) . Previously it's been found by the same group that the strongest risk-associated SNPs fall within the enhancer region named PRE1 that regulates the expression of CCND1 . PRE1 also acts as an enhancer on the lncRNAs CUPID1 and CUPID2 which are transcribed from a bidirectional promoter. The two lncRNAs were highly expressed in breast cancer cell lines dependent on estrogen . However, this induction was not associated with PRE1 region amplification, indicating that copy-number variation is not the only mechanism underlying the expression. Unlike CCND1, silencing of CUPID1 or CUPID2 did not affect cell cycle, although depletion of these two lncRNAs indeed caused deregulation of DNA replication, recombination and repair genes . The authors have illustrated that CUPID1 and CUPID2 can facilitate the formation of phosphorylated RPA foci and promote RAD51 recruitment to DSBs during the initiation step of the HR pathway. Interestingly, when breast cancer risk SNPs were incorporated into PRE1 region, leading to the decreased expression of these two lncRNAs, the overall DSB repair was not impeded, but a large number of structural variants across the genome were observed . These data proposed a clear regulatory role for these two lncRNAs: CUPID1 and CUPID2 prevent the breast tumors from error introduction in response to radiotherapy by favoring a switch from NHEJ to HR DSB repair.