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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11688-11699
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11688
Colitis-associated colon cancer: Is it in your genes?
Lauren Van Der Kraak, Philippe Gros, Nicole Beauchemin
Lauren Van Der Kraak, Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montréal, QC H3G 1Y6, Canada
Philippe Gros, Department of Biochemistry and Complex Trait Group, McGill University, Montréal, QC H3G 0B1, Canada
Nicole Beauchemin, Departments of Biochemistry, Medicine and Oncology and Goodman Cancer Research Centre, McGill University, Montréal, QC H3G 1Y6, Canada
Author contributions: Van Der Kraak L, Gros P and Beauchemin N compiled the research and wrote the paper.
Supported by The Cancer Research Society, No. 19490 (to Beauchemin N and Gros P). Van Der Kraak L is the recipient of a Canadian Institute of Health Research Doctoral Award (PA-Digestive Health) and a McGill Integrated Cancer Research Training Program studentship.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nicole Beauchemin, PhD, Departments of Biochemistry, Medicine and Oncology and Goodman Cancer Research Centre, McGill University, McIntyre Building, Room 702A, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, Canada. nicole.beauchemin@mcgill.ca
Telephone: +1-514-3983541 Fax: +1-514-3986769
Received: April 27, 2015
Peer-review started: May 4, 2015
First decision: June 23, 2015
Revised: July 4, 2015
Accepted: September 15, 2015
Article in press: September 15, 2015
Published online: November 7, 2015
Processing time: 189 Days and 18 Hours
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.

Keywords: Colitis-associated colorectal cancer; Inflammatory bowel disease; Forward genetics; Susceptibility genes; Azoxymethane; Dextran sulfate sodium; Mouse models

Core tip: Colitis-associated colorectal cancer (CA-CRC) is the cause of death in 10%-15% of inflammatory bowel disease (IBD) patients. Quantitative estimates of overall CA-CRC risk are highly variable and depend of the severity, duration and location of active IBD. 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. 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.