Prior to analysis for novel shared germline variants, a targeted analysis was undertaken of 17 genes associated with an increased familial colorectal cancer risk: APC, MUTYH, MLH1, MSH2, MSH6, PMS2, BMPR1A, SMAD4, STK11, EPCAM [32], GREM1, POLE [33], POLD1 [33], BUB1 [34], BUB1B [35], BUB3 [34] and NTHL1 [36]. This evidence concerns the gene SMAD4 and colorectal cancer.