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- gastrointestinal neoplasia
- colorectal cancer
- chronic inflammation
- JC virus
- viral oncogenesis
- DNA mismatch repair
- p53
- inflammatory bowel disease
- mutagenesis
- microsatellite instability
INTRODUCTION
The struggle to understand the origins of human cancers has captured the imagination of many investigators. The epidemiology of human cancers and the availability of many laboratory models of cancer could give the casual observer the impression that all cancers are a result of exposures to chemical carcinogens in the environment. This is only part of the story, and in most instances environmental exposures are very different in scale from what is required in laboratory animals to induce tumours. Actually, most laboratory models have been carefully developed to match the carcinogen with the host. For example, several alkylating agents can induce intestinal cancers in rodents.1 However, the distribution of the neoplasms throughout the gut varies from one mouse strain to another, and in some instances the carcinogens induce tumours only outside the gut. Lower doses—perhaps those more relevant for human cancers—may be tolerated, and not induce cancer at all. The mechanisms for tumour development in the human gastrointestinal tract appear to be a much more complicated issue.
This review of recent advances in basic science will focus on newly discovered mechanisms involved in the development of colorectal cancer (CRC). This is potentially a very broad topic, and therefore we have selected two novel mechanisms for emphasis. Firstly, a virus carried by most healthy individuals has been implicated as a possible cause for chromosomal instability (CIN), the process that leads to aneuploidy. Chromosomal aberrations and this form of genomic instability play a major role in the development and progression of multistep carcinogenesis, such as occurs in CRC.2 Secondly, it is abundantly clear that inflammation is carcinogenic, and furthermore, endogenous processes that can modify the ability of the host to cope with inflammation appear to modify the risk of cancer to the host. There is growing evidence that this may …
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Conflict of interest: None declared.