title: Colitis-associated colon cancer: Is it in your genes?
abstract: Colitis-associated colorectal cancer (CA-CRC) is the cause of death in 10%-15% of inflammatory bowel disease (IBD) patients. CA-CRC results from the accumulation of mutations in intestinal epithelial cells and progresses through a well-characterized inflammation to dysplasia to carcinoma sequence. Quantitative estimates of overall CA-CRC risks are highly variable ranging from 2% to 40% depending on IBD severity, duration and location, with IBD duration being the most significant risk factor associated with CA-CRC development. Recently, studies have identified IBD patients with similar patterns of colonic inflammation, but that differ with respect to CA-CRC development, suggesting a role for additional non-inflammatory risk factors in CA-CRC development. One suggestion is that select IBD patients carry polymorphisms in various low penetrance disease susceptibility genes, which pre-dispose them to CA-CRC development, although these loci have proven difficult to identify in human genome-wide association studies. Mouse models of CA-CRC have provided a viable alternative for the discovery, validation and study of individual genes in CA-CRC pathology. In this review, we summarize the current CA-CRC literature with a strong focus on genetic pre-disposition and highlight an emerging role for mouse models in the search for CA-CRC risk alleles.
authors.affiliation: Lauren Van Der Kraak, Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, QC H3G 1Y6, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Van Der Kraak
authors.affiliation: Lauren Van Der Kraak, Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, QC H3G 1Y6, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
authors.affiliation: Lauren Van Der Kraak, Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, QC H3G 1Y6, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology; D003092:Colitis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D010641:Phenotype; D012307:Risk Factors
keywords: Azoxymethane; Colitis-associated colorectal cancer; Dextran sulfate sodium; Forward genetics; Inflammatory bowel disease; Mouse models; Susceptibility genes