While the mechanism linking the 7p14.3 variant and SPOP mutation remains elusive and future studies should investigate the role of the allele in the emergence of SPOP somatic mutations, we propose a relevant role in cancer predisposition of non-coding variants that lead to allele-specific transactivation of central TF programs with age dependent and tissue-specific effect8, 21, 25 manifesting in early somatic genomic events. Here, SPOP is linked to cancer.