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British Medical Bulletin 64:27-43 (2002)
© 2002 The British Council
Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis
* Cancer Research UK, Weatherall Institute of Molecular Medicine, Oxford, UK
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK
Familial adenomatous polyposis and hereditary non-polyposis colorectal cancer are dominantly inherited conditions with 100% and 80% life-time risk of developing colorectal cancer, respectively. The genetic mutations responsible for these two conditions lie in the adenomatous polyposis coli (APC) and mismatch repair genes. These same genes also play a key role in the formation of sporadic colorectal cancers, which arise on a background of a similar spectrum of mutations to the hereditary cancers. This article examines the genetic mechanisms underlying the hereditary colorectal cancers, as well as genetic predisposition to colorectal cancer in the general population in the absence of a clear-cut genetic syndrome.
Colorectal cancer arises as the cumulative effect of multiple mutations within the cell, allowing it to escape growth and regulatory control mechanisms. This step-wise progression of mutations facilitates the histological transition from normal mucosa to adenoma to carcinoma. The latter part of this paper focuses on the key genetic events underlying this process and provides an overview of the genetic mechanisms responsible for colorectal tumorigenesis.
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