Given that common polymorphisms have been addressed by CRC and EC GWAS, the uncharacterized germline risk variants are likely to be individually uncommon (<5% allele frequency) and some may not necessarily be in the exonuclease domains of POLE and POLD1. It will be necessary to obtain evidence for their effects using a variety of functional assays. The gene discussed is POLD1; the disease is colorectal carcinoma.