It is likely that many of the cancer risk loci found by COGS influence gene regulation, as ~66% of confirmed susceptibility alleles lie within or near genes, with only 5% located within coding regions. Subsequent functional annotation and experimental studies therefore have sought spatial association with transcription factor binding sites, histone modifications or other putative regulatory elements. However, in vitro functional studies in a relevant tissue and cell type, as well as in vivo studies in model organisms, are also needed to provide insight into the mechanisms underlying the development of breast, ovarian and prostate cancers.