For example, although FAP patients usually develop hundreds or thousands of adenomas, a few individuals with variants in proximal, distal or alternatively spliced regions of the gene have so-called attenuated disease, with tens or fewer tumours.4 The position of the germline APC variants also influences the ‘classical' (>100 adenomas) FAP phenotype: for example, severe colonic polyposis is associated with germline variants near codon 1309.5 However, several studies have also addressed the possibility that modifier genes unlinked to APC influence the FAP phenotype.6, 7, 8. This evidence concerns the gene APC and adenoma.