title: Chronic inflammation, colorectal cancer and gene polymorphisms.
abstract: Chronic inflammation is commonly present in gastrointestinal mucosal sites at increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic gastritis caused by Helicobacter pylori infection. Why some patients have more mucosal inflammation than others, and why certain individuals with chronic inflammation develop cancer, are problems that have not been solved. Unlike the case for the syndromic forms of familial colorectal cancer (CRC), the risks for IBD and other forms of chronic inflammation have not been linked to highly penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are variations in DNA sequence that can be linked to any phenotype (cancer, chronic inflammation, etc.) in genome-wide association studies (GWAS). CRC has been linked to several highly penetrant single gene loci, as well as multiple SNP. The propensity to develop IBD has not been linked to single gene mutations in most instances, but has been linked to SNP in the NOD2 locus (which appear to create hypomorphic alleles for this bacterial response gene), the IL23R locus, the autophagy gene ATG16L1 and a wide range of other loci including the Toll-like receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in predicting risk for chronic inflammation is that there are many genetic polymorphisms with relatively modest individual effects. Our challenge is to understand how the SNPs that are linked to variations in the inflammatory response interact with one another (i.e. to understand the 'epistasis' involved), and to integrate this with the variety of individual environmental exposures. This represents an opportunity for informatics science to help personalize our approach to chronic inflammatory diseases of the gut and identify those at greatest risk for cancer.
authors.affiliation: Division of Gastroenterology, Baylor University Medical Center, GI Cancer Research Laboratory, Dallas, TX 75246, USA. rickbo@baylorhealth.edu
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
mesh_terms: D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000150:complications* / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000235:genetics; D043183:Irritable Bowel Syndrome / Q000235:genetics; D019683:Penetrance; D011110:Polymorphism, Genetic