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Genetic risk for colitis-associated colorectal cancer
  1. Edus H Warren1,2
  1. 1
    Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  2. 2
    Department of Medicine, University of Washington, Seattle, Washington, USA
  1. Correspondence to Dr Edus H Warren, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D3-100, PO Box 19024, Seattle, WA 98109-1024, USA; ehwarren{at}u.washington.edu

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The development of colorectal cancer (CRC) is arguably the most feared complication of ulcerative colitis. Clinical variables correlated with the development of CRC in patients with ulcerative colitis include age at onset, duration and geographical extent of disease, and concomitant primary sclerosing cholangitis (PSC). Patients with ulcerative colitis and with extensive duration of disease or pancolitis have a cumulative lifetime risk of CRC that exceeds 30%.1 Although the pathogenesis of CRC that develops in patients with ulcerative colitis is poorly understood, several studies have identified molecular features that distinguish CRC associated with ulcerative colitis from sporadic CRC.2 3 4 5 CRC that develops in patients with ulcerative colitis is most common in the rectum and sigmoid colon, almost always occurs in areas involved by chronic inflammation, and is more frequently characterised by multiple synchronous tumours than is sporadic CRC.6 It is generally preceded by dysplasia, which therefore provides cogent rationale for colonoscopic surveillance for CRC in patients with ulcerative colitis, particularly those with pancolitis and extended duration of disease.

Although a large number of germline and somatic genetic lesions have been associated with a predisposition to the development of CRC, little is known about the extent to which genetic factors may influence the risk for development of CRC in patients with ulcerative colitis. In this issue of Gut, Garrity-Park and colleagues7 (see page 1226) now report that risk for the development of CRC in patients with ulcerative colitis is associated with specific HLA-DR and HLA-DQ alleles encoded at loci within the class II region of the major histocompatibility complex (MHC) on chromosome 6p. The HLA-DR and HLA-DQ molecules are heterodimeric cell surface proteins that present polypeptide antigens derived primarily from extracellular sources to CD4+ T lymphocytes, and play multiple critical roles in adaptive immunity. …

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