However, the only detailed genomic association with aetiological risk factors investigated by genome sequencing has been the association with liver fluke infection (Opisthorchis viverrini and Clonorchis sinensis), with fluke-positive tumours showing an overall higher mutational rate (median 4,700 versus 3,143 somatic mutations per tumour)116 with prevalent mutations in SMAD4 and TP53 as well as ERBB2 amplifications116–118. This evidence concerns the gene SMAD4 and neoplasm.