title: Inherited predisposition to colorectal cancer: towards a more complete picture.
abstract: Colorectal carcinoma (CRC) is the third most common cancer worldwide. Hereditary factors are important in 15%-35% of affected patients. This review provides an update on the genetic basis of inherited predisposition to CRC. Currently known genetic factors include a group of highly penetrant mutant genes associated with rare mendelian cancer syndromes and a group of common low-penetrance alleles that have been identified through genetic association studies. Additional mechanisms, which may underlie a predisposition to CRC, will be outlined, for example, variants in intermediate penetrance alleles. Recent findings, including mutations in POLE, POLD1 and NTHL1, will be highlighted, and we identify gaps in present knowledge and consider how these may be addressed through current and emerging genomic approaches. It is expected that identification of the missing heritable component of CRC will be resolved through evermore comprehensive cataloguing and phenotypic annotation of CRC-associated variants identified through sequencing approaches. This will have important clinical implications, particularly in areas such as risk stratification, public health and CRC prevention.
authors: Institute of Cancer and Genetics, Cardiff University, Heath Park Campus, Cardiff, UK.
authors: Emma
authors: E
authors: Short
authors: Institute of Cancer and Genetics, Cardiff University, Heath Park Campus, Cardiff, UK.
authors: Laura E
authors: LE
authors: Thomas
authors: Department of Gastroenterology, Cwm Taf University Health Board, Prince Charles Hospital, Merthyr Tydfil, UK.
authors: Joanna
authors: J
authors: Hurley
authors: Institute of Medical Genetics, Cardiff and Vale Health Board, Cardiff, UK.
authors: Sian
authors: S
authors: Jose
authors: Institute of Cancer and Genetics, Cardiff University, Heath Park Campus, Cardiff, UK.
authors: Julian R
authors: JR
authors: Sampson
mesh_terms: D000483:Alleles; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D019683:Penetrance; D012307:Risk Factors
keywords: Cancer: colon; Clinical genetics; Gastroenterology; Genetics