Genetic predisposition to gastrointestinal polyposis: syndromes, tumour features, genetic testing, and clinical management

Abstract

Gastrointestinal tract polyposis is characterised by the presence of multiple polyps, particularly in the colorectum, and encompasses both cancer predisposition genetic syndromes and non-syndromic clinical manifestations. The sources of the heterogeneity observed in polyposis syndromes relate to genetic cause, mode of inheritance, polyp burden and histological type, and spectrum and frequency of extracolonic manifestations. These features determine the clinical management of carriers, including strategies for cancer prevention and early detection, and oncological treatments. Despite substantial progress in identifying the genetic causes of polyposis, a large proportion of cases remain genetically unexplained. Although some of these cases might be due to lifestyle, environmental factors, or cancer treatments, it is likely that additional polyposis predisposition genes will be identified. This Review provides an overview of the known syndromes and genes, genetic testing, and clinical management of patients with polyposis, and recent advances and challenges in the field of gastrointestinal polyposis.