Dataset Information

Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study.

ABSTRACT:

Background & aims

An association between inflammatory activity and colorectal neoplasia (CRN) has been documented in patients with ulcerative colitis (UC). However, previous studies did not address the duration of inflammation or the effects of therapy on risk for CRN. We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN.

Methods

We collected data from 141 patients with UC without CRN (controls) and 59 matched patients with UC who developed CRN (cases), comparing disease extent and duration and patients' ages. We used a new 6-point histologic inflammatory activity (HIA) scale to score biopsy fragments (n = 4449). Information on medications, smoking status, primary sclerosing cholangitis, and family history of CRN were collected from the University of Chicago Inflammatory Bowel Disease Endoscopy Database. Relationships between HIA, clinical features, and CRN were assessed by conditional logistic regression.

Results

Cases and controls were similar in numbers of procedures and biopsies, exposure to steroids or mesalamine, smoking status, and family history of CRN. They differed in proportion of men vs women, exposure to immune modulators, and primary sclerosing cholangitis prevalence. In univariate analysis, HIA was positively associated with CRN (odds ratio [OR], 2.56 per unit increase; P = .001), whereas immune modulators (including azathioprine, 6-mercaptopurine, and methotrexate) reduced the risk for CRN (OR, 0.35; P < .01). HIA was also associated with CRN in multivariate analysis (OR, 3.68; P = .001).

Conclusions

In a case-control study, we associated increased inflammation with CRN in patients with UC. Use of immune modulators reduced the risk for CRN, indicating that these drugs have chemoprotective effects. On the basis of these data, we propose new stratified surveillance and treatment strategies to prevent and detect CRN in patients with UC.

SUBMITTER: Rubin DT

PROVIDER: S-EPMC3840031 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study.

Rubin David T DT Huo Dezheng D Kinnucan Jami A JA Sedrak Mina S MS McCullom Nicole E NE Bunnag Alana P AP Raun-Royer Elin P EP Cohen Russell D RD Hanauer Stephen B SB Hart John J Turner Jerrold R JR

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20130717 12

<h4>Background & aims</h4>An association between inflammatory activity and colorectal neoplasia (CRN) has been documented in patients with ulcerative colitis (UC). However, previous studies did not address the duration of inflammation or the effects of therapy on risk for CRN. We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN.<h4>Methods</h4>We collected data from 141 patients with UC without CRN (controls) and 59 matched patien ...[more]

PMID: 23872237

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Project description:Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) presumably caused by dysregulated immune responses to the gut microbiota. Genetic association studies have implicated dozens of chromosomal regions or loci in IBD susceptibility. The next challenge is to explain the individual role of each of these modest effect loci in the disease state. We have previously identified MAST3 as an IBD susceptibility gene through genetic fine-mapping of the 19p linkage region. Testing MAST3 in a reporter assay provided preliminary evidence that MAST3 modulates the activity of inflammation-related transcription factor nuclear factor kappa B.Here we characterized the function of MAST3 through an examination of the influence of the modulation of MAST3 expression on endogenous genome-wide expression patterns. More specifically, we looked at differential gene expression resulting from overexpression and knockdown of the MAST3 gene in epithelial and macrophage cell lines. From we highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-jB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD.We highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-?B activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. These MAST3-regulated genes are central to mucosal immune responses. Among them are proinflammatory cytokines (e.g., CCL20, IL8), regulators of NF-?B (e.g., TNFAIP3, LY96, NFKBIA), genes involved in interferon-induced defense against pathogen invasion (e.g., IFIT1, ISG15), and genes involved in cell adhesion and/or migration (e.g., CD44, TMOD1).Taken together, these results confirm MAST3 as a modulator of the inflammatory response through regulation of immune gene expression in the gut of IBD patients.

Dataset Information

Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study.

Background & aims

Methods

Results

Conclusions

Publications

Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study.

Similar Datasets

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