title: Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, Illinois. Electronic address: drubin@medicine.bsd.uchicago.edu.
authors.forename: David T
authors.initials: DT
authors.lastname: Rubin
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Jami A
authors.initials: JA
authors.lastname: Kinnucan
authors.forename: Mina S
authors.initials: MS
authors.lastname: Sedrak
authors.forename: Nicole E
authors.initials: NE
authors.lastname: McCullom
authors.forename: Alana P
authors.initials: AP
authors.lastname: Bunnag
authors.forename: Elin P
authors.initials: EP
authors.lastname: Raun-Royer
authors.forename: Russell D
authors.initials: RD
authors.lastname: Cohen
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hanauer
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications* / Q000473:pathology*; D003110:Colonic Neoplasms / Q000453:epidemiology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
keywords: 6-MP; 6-mercaptopurine; 6MP; AOR; AZA; CI; CRC; CRN; Chemoprevention; Colorectal Cancer; Dysplasia; HIA; IBD; Mesalamine; OR; PSC; UC; adjusted odds ratio; colorectal cancer; colorectal neoplasia; confidence interval; histologic inflammatory activity; inflammatory bowel disease; odds ratio; primary sclerosing cholangitis; ulcerative colitis