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Genetic Instability and Chronic Inflammation in Gastrointestinal Cancers

  • Antonia R. Sepulveda
  • John P. Lynch
Chapter
Part of the Cancer Genetics book series (CANGENETICS)

Abstract

Genetic instability and inflammation are closely intertwined processes. While the induction of genetic instability in the setting of inflammation is easy to conceptualize, the reverse occurs as well. It has been appreciated for some time now that colon cancers that arise in the setting of DNA mismatch repair (MMR) deficiencies have a significant lymphocyte infiltration, suggesting an inflammatory response. This characteristic is being used clinically by pathologists to identify the approximately 15% of human colon cancers that develop with microsatellite instability (MSI) rather than the more common chromosomal instability. Inactivating mutations or gene silencing of hMLH1 or hMSH2, which are essential for normal MMR, are frequently observed in these cancers and account for the vast majority of hereditary non-polyposis colorectal cancer (HNPCC, or Lynch syndrome I) (Ionov et al. 1993; Thibodeau et al. 1993; Fishel et al. 1993; Leach et al. 1993). How the induction of MSI leads to the increased inflammatory response remains unknown. What is better understood is how chronic inflammatory processes provoke genetic instabilities that lead to the development of cancer.

Keywords

Gastric Cancer Ulcerative Colitis Pylorus Infection Adenomatous Polyposis Coli Lynch Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Hospital of the University of PennsylvaniaPennsylvaniaUSA
  2. 2.Division of Gastroenterology/650 CRBPhiladelphiaUSA

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