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 progresse...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 predispose them to CA-CRC development, although these loci have proven difficult to identify in human genomewide 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 predisposition and highlight an emerging role for mouse models in the search for CA-CRC risk alleles.展开更多
基金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 Mc Gill Integrated Cancer Research Training Program studentship
文摘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 predispose them to CA-CRC development, although these loci have proven difficult to identify in human genomewide 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 predisposition and highlight an emerging role for mouse models in the search for CA-CRC risk alleles.
